Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome
Identifieur interne : 002425 ( Istex/Corpus ); précédent : 002424; suivant : 002426Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome
Auteurs : Christopher T. Gordon ; Alice Vuillot ; Sandrine Marlin ; Erica Gerkes ; Alex Henderson ; Adila Alkindy ; Muriel Holder-Espinasse ; Sarah S. Park ; Asma Omarjee ; Mateo Sanchis-Borja ; Eya Ben Bdira ; Myriam Oufadem ; Birgit Sikkema-Raddatz ; Alison Stewart ; Rodger Palmer ; Ruth Mcgowan ; Florence Petit ; Bruno Delobel ; Michael R. Speicher ; Paul Aurora ; David Kilner ; Philippe Pellerin ; Marie Simon ; Jean-Paul Bonnefont ; Edward S. Tobias ; Sixto García-Mi Aúr ; Maria Bitner-Glindzicz ; Pernille Lindholm ; Brigitte A. Meijer ; Véronique Abadie ; Françoise Denoyelle ; Marie-Paule Vazquez ; Christa Rotky-Fast ; Vincent Couloigner ; Sébastien Pierrot ; Yves Manach ; Sylvain Breton ; Yvonne M C. Hendriks ; Arnold Munnich ; Linda Jakobsen ; Peter Kroisel ; Angela Lin ; Leonard B. Kaban ; Lina Basel-Vanagaite ; Louise Wilson ; Michael L. Cunningham ; Stanislas Lyonnet ; Jeanne AmielSource :
- Journal of Medical Genetics [ 0022-2593 ] ; 2013-03.
Abstract
Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, β 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.
Url:
DOI: 10.1136/jmedgenet-2012-101331
Links to Exploration step
ISTEX:7348F3B9E6763856063CA42E9C7451B169BAE498Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome</title>
<author><name sortKey="Gordon, Christopher T" sort="Gordon, Christopher T" uniqKey="Gordon C" first="Christopher T" last="Gordon">Christopher T. Gordon</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Vuillot, Alice" sort="Vuillot, Alice" uniqKey="Vuillot A" first="Alice" last="Vuillot">Alice Vuillot</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Marlin, Sandrine" sort="Marlin, Sandrine" uniqKey="Marlin S" first="Sandrine" last="Marlin">Sandrine Marlin</name>
<affiliation><mods:affiliation>Centre de référence des surdités génétiques, Service de génétique médicale, Hôpital d'Enfants Armand-Trousseau AP-HP, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Gerkes, Erica" sort="Gerkes, Erica" uniqKey="Gerkes E" first="Erica" last="Gerkes">Erica Gerkes</name>
<affiliation><mods:affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Henderson, Alex" sort="Henderson, Alex" uniqKey="Henderson A" first="Alex" last="Henderson">Alex Henderson</name>
<affiliation><mods:affiliation>Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Alkindy, Adila" sort="Alkindy, Adila" uniqKey="Alkindy A" first="Adila" last="Alkindy">Adila Alkindy</name>
<affiliation><mods:affiliation>Department of Genetics, Sultan Qaboos University Hospital, Muscat, Oman</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Holder Espinasse, Muriel" sort="Holder Espinasse, Muriel" uniqKey="Holder Espinasse M" first="Muriel" last="Holder-Espinasse">Muriel Holder-Espinasse</name>
<affiliation><mods:affiliation>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Park, Sarah S" sort="Park, Sarah S" uniqKey="Park S" first="Sarah S" last="Park">Sarah S. Park</name>
<affiliation><mods:affiliation>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Omarjee, Asma" sort="Omarjee, Asma" uniqKey="Omarjee A" first="Asma" last="Omarjee">Asma Omarjee</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Sanchis Borja, Mateo" sort="Sanchis Borja, Mateo" uniqKey="Sanchis Borja M" first="Mateo" last="Sanchis-Borja">Mateo Sanchis-Borja</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Bdira, Eya Ben" sort="Bdira, Eya Ben" uniqKey="Bdira E" first="Eya Ben" last="Bdira">Eya Ben Bdira</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Oufadem, Myriam" sort="Oufadem, Myriam" uniqKey="Oufadem M" first="Myriam" last="Oufadem">Myriam Oufadem</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Sikkema Raddatz, Birgit" sort="Sikkema Raddatz, Birgit" uniqKey="Sikkema Raddatz B" first="Birgit" last="Sikkema-Raddatz">Birgit Sikkema-Raddatz</name>
<affiliation><mods:affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Stewart, Alison" sort="Stewart, Alison" uniqKey="Stewart A" first="Alison" last="Stewart">Alison Stewart</name>
<affiliation><mods:affiliation>West Midlands Regional Genetics Service, Birmingham, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Palmer, Rodger" sort="Palmer, Rodger" uniqKey="Palmer R" first="Rodger" last="Palmer">Rodger Palmer</name>
<affiliation><mods:affiliation>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Mcgowan, Ruth" sort="Mcgowan, Ruth" uniqKey="Mcgowan R" first="Ruth" last="Mcgowan">Ruth Mcgowan</name>
<affiliation><mods:affiliation>North Scotland Regional Genetics Service, Ashgrove House, Aberdeen, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Petit, Florence" sort="Petit, Florence" uniqKey="Petit F" first="Florence" last="Petit">Florence Petit</name>
<affiliation><mods:affiliation>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Delobel, Bruno" sort="Delobel, Bruno" uniqKey="Delobel B" first="Bruno" last="Delobel">Bruno Delobel</name>
<affiliation><mods:affiliation>Laboratoire de génétique chromosomique, Hôpital St Vincent de Paul, Lille, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Speicher, Michael R" sort="Speicher, Michael R" uniqKey="Speicher M" first="Michael R" last="Speicher">Michael R. Speicher</name>
<affiliation><mods:affiliation>Institute of Human Genetics, Medical University of Graz, Graz, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Aurora, Paul" sort="Aurora, Paul" uniqKey="Aurora P" first="Paul" last="Aurora">Paul Aurora</name>
<affiliation><mods:affiliation>Respiratory Medicine, Great Ormond Street Hospital, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kilner, David" sort="Kilner, David" uniqKey="Kilner D" first="David" last="Kilner">David Kilner</name>
<affiliation><mods:affiliation>Respiratory Medicine, Great Ormond Street Hospital, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Pellerin, Philippe" sort="Pellerin, Philippe" uniqKey="Pellerin P" first="Philippe" last="Pellerin">Philippe Pellerin</name>
<affiliation><mods:affiliation>Centre de Référence des Malformations Cranio-maxillo-faciales Rares, CHRU Lille, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Simon, Marie" sort="Simon, Marie" uniqKey="Simon M" first="Marie" last="Simon">Marie Simon</name>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Bonnefont, Jean Paul" sort="Bonnefont, Jean Paul" uniqKey="Bonnefont J" first="Jean-Paul" last="Bonnefont">Jean-Paul Bonnefont</name>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Tobias, Edward S" sort="Tobias, Edward S" uniqKey="Tobias E" first="Edward S" last="Tobias">Edward S. Tobias</name>
<affiliation><mods:affiliation>School of Medicine, University of Glasgow, Yorkhill Hospital, Glasgow, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Garcia Mi Aur, Sixto" sort="Garcia Mi Aur, Sixto" uniqKey="Garcia Mi Aur S" first="Sixto" last="García-Mi Aúr">Sixto García-Mi Aúr</name>
<affiliation><mods:affiliation>Institute for Medical and Molecular Genetics, La Paz University Hospital, Madrid, Spain</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Bitner Glindzicz, Maria" sort="Bitner Glindzicz, Maria" uniqKey="Bitner Glindzicz M" first="Maria" last="Bitner-Glindzicz">Maria Bitner-Glindzicz</name>
<affiliation><mods:affiliation>Clinical and Molecular Genetics, Institute of Child Health, UCL, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lindholm, Pernille" sort="Lindholm, Pernille" uniqKey="Lindholm P" first="Pernille" last="Lindholm">Pernille Lindholm</name>
<affiliation><mods:affiliation>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Meijer, Brigitte A" sort="Meijer, Brigitte A" uniqKey="Meijer B" first="Brigitte A" last="Meijer">Brigitte A. Meijer</name>
<affiliation><mods:affiliation>Department of Oral and Maxillofacial Surgery, Kennemer Gasthuis, Haarlem, The Netherlands</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Abadie, Veronique" sort="Abadie, Veronique" uniqKey="Abadie V" first="Véronique" last="Abadie">Véronique Abadie</name>
<affiliation><mods:affiliation>Service de Pédiatrie Générale, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Denoyelle, Francoise" sort="Denoyelle, Francoise" uniqKey="Denoyelle F" first="Françoise" last="Denoyelle">Françoise Denoyelle</name>
<affiliation><mods:affiliation>INSERM UMR-S587 and Pediatric Otolaryngology Department, Armand-Trousseau Children's Hospital, AP-HP, Paris 6 University, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Vazquez, Marie Paule" sort="Vazquez, Marie Paule" uniqKey="Vazquez M" first="Marie-Paule" last="Vazquez">Marie-Paule Vazquez</name>
<affiliation><mods:affiliation>Service de Chirurgie Maxillo-Faciale et Plastique, CRMR des Malformations de la Face et de la Cavité Buccale, Hôpital Necker-Enfants Malades, AP-HP, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Université Paris 5, UFR de Médecine Paris-Descartes, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Centre de Recherche des Cordeliers, UMR S 872, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Rotky Fast, Christa" sort="Rotky Fast, Christa" uniqKey="Rotky Fast C" first="Christa" last="Rotky-Fast">Christa Rotky-Fast</name>
<affiliation><mods:affiliation>Department of Pediatrics and Adolescence Medicine, Medical University of Graz, Graz, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Couloigner, Vincent" sort="Couloigner, Vincent" uniqKey="Couloigner V" first="Vincent" last="Couloigner">Vincent Couloigner</name>
<affiliation><mods:affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Pierrot, Sebastien" sort="Pierrot, Sebastien" uniqKey="Pierrot S" first="Sébastien" last="Pierrot">Sébastien Pierrot</name>
<affiliation><mods:affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Manach, Yves" sort="Manach, Yves" uniqKey="Manach Y" first="Yves" last="Manach">Yves Manach</name>
<affiliation><mods:affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Breton, Sylvain" sort="Breton, Sylvain" uniqKey="Breton S" first="Sylvain" last="Breton">Sylvain Breton</name>
<affiliation><mods:affiliation>AP-HP, Service d'Imagerie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Laboratoire d'Anatomie, Université Paris-Descartes, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Hendriks, Yvonne M C" sort="Hendriks, Yvonne M C" uniqKey="Hendriks Y" first="Yvonne M C" last="Hendriks">Yvonne M C. Hendriks</name>
<affiliation><mods:affiliation>Department of Clinical Genetics, Free University Medical Center, Amsterdam, The Netherlands</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Munnich, Arnold" sort="Munnich, Arnold" uniqKey="Munnich A" first="Arnold" last="Munnich">Arnold Munnich</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Jakobsen, Linda" sort="Jakobsen, Linda" uniqKey="Jakobsen L" first="Linda" last="Jakobsen">Linda Jakobsen</name>
<affiliation><mods:affiliation>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kroisel, Peter" sort="Kroisel, Peter" uniqKey="Kroisel P" first="Peter" last="Kroisel">Peter Kroisel</name>
<affiliation><mods:affiliation>Institute of Human Genetics, Medical University of Graz, Graz, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lin, Angela" sort="Lin, Angela" uniqKey="Lin A" first="Angela" last="Lin">Angela Lin</name>
<affiliation><mods:affiliation>Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kaban, Leonard B" sort="Kaban, Leonard B" uniqKey="Kaban L" first="Leonard B" last="Kaban">Leonard B. Kaban</name>
<affiliation><mods:affiliation>Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Basel Vanagaite, Lina" sort="Basel Vanagaite, Lina" uniqKey="Basel Vanagaite L" first="Lina" last="Basel-Vanagaite">Lina Basel-Vanagaite</name>
<affiliation><mods:affiliation>Pediatric Genetics, Schneider Children's Medical Center of Israel and Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Wilson, Louise" sort="Wilson, Louise" uniqKey="Wilson L" first="Louise" last="Wilson">Louise Wilson</name>
<affiliation><mods:affiliation>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Cunningham, Michael L" sort="Cunningham, Michael L" uniqKey="Cunningham M" first="Michael L" last="Cunningham">Michael L. Cunningham</name>
<affiliation><mods:affiliation>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Department of Pediatrics, University of Washington and Seattle Children's Hospital Craniofacial Center, Seattle, Washington, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lyonnet, Stanislas" sort="Lyonnet, Stanislas" uniqKey="Lyonnet S" first="Stanislas" last="Lyonnet">Stanislas Lyonnet</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Amiel, Jeanne" sort="Amiel, Jeanne" uniqKey="Amiel J" first="Jeanne" last="Amiel">Jeanne Amiel</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:7348F3B9E6763856063CA42E9C7451B169BAE498</idno>
<date when="2013" year="2013">2013</date>
<idno type="doi">10.1136/jmedgenet-2012-101331</idno>
<idno type="url">https://api.istex.fr/document/7348F3B9E6763856063CA42E9C7451B169BAE498/fulltext/pdf</idno>
<idno type="wicri:Area/Istex/Corpus">002425</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002425</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a">Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome</title>
<author><name sortKey="Gordon, Christopher T" sort="Gordon, Christopher T" uniqKey="Gordon C" first="Christopher T" last="Gordon">Christopher T. Gordon</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Vuillot, Alice" sort="Vuillot, Alice" uniqKey="Vuillot A" first="Alice" last="Vuillot">Alice Vuillot</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Marlin, Sandrine" sort="Marlin, Sandrine" uniqKey="Marlin S" first="Sandrine" last="Marlin">Sandrine Marlin</name>
<affiliation><mods:affiliation>Centre de référence des surdités génétiques, Service de génétique médicale, Hôpital d'Enfants Armand-Trousseau AP-HP, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Gerkes, Erica" sort="Gerkes, Erica" uniqKey="Gerkes E" first="Erica" last="Gerkes">Erica Gerkes</name>
<affiliation><mods:affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Henderson, Alex" sort="Henderson, Alex" uniqKey="Henderson A" first="Alex" last="Henderson">Alex Henderson</name>
<affiliation><mods:affiliation>Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Alkindy, Adila" sort="Alkindy, Adila" uniqKey="Alkindy A" first="Adila" last="Alkindy">Adila Alkindy</name>
<affiliation><mods:affiliation>Department of Genetics, Sultan Qaboos University Hospital, Muscat, Oman</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Holder Espinasse, Muriel" sort="Holder Espinasse, Muriel" uniqKey="Holder Espinasse M" first="Muriel" last="Holder-Espinasse">Muriel Holder-Espinasse</name>
<affiliation><mods:affiliation>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Park, Sarah S" sort="Park, Sarah S" uniqKey="Park S" first="Sarah S" last="Park">Sarah S. Park</name>
<affiliation><mods:affiliation>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Omarjee, Asma" sort="Omarjee, Asma" uniqKey="Omarjee A" first="Asma" last="Omarjee">Asma Omarjee</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Sanchis Borja, Mateo" sort="Sanchis Borja, Mateo" uniqKey="Sanchis Borja M" first="Mateo" last="Sanchis-Borja">Mateo Sanchis-Borja</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Bdira, Eya Ben" sort="Bdira, Eya Ben" uniqKey="Bdira E" first="Eya Ben" last="Bdira">Eya Ben Bdira</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Oufadem, Myriam" sort="Oufadem, Myriam" uniqKey="Oufadem M" first="Myriam" last="Oufadem">Myriam Oufadem</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Sikkema Raddatz, Birgit" sort="Sikkema Raddatz, Birgit" uniqKey="Sikkema Raddatz B" first="Birgit" last="Sikkema-Raddatz">Birgit Sikkema-Raddatz</name>
<affiliation><mods:affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Stewart, Alison" sort="Stewart, Alison" uniqKey="Stewart A" first="Alison" last="Stewart">Alison Stewart</name>
<affiliation><mods:affiliation>West Midlands Regional Genetics Service, Birmingham, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Palmer, Rodger" sort="Palmer, Rodger" uniqKey="Palmer R" first="Rodger" last="Palmer">Rodger Palmer</name>
<affiliation><mods:affiliation>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Mcgowan, Ruth" sort="Mcgowan, Ruth" uniqKey="Mcgowan R" first="Ruth" last="Mcgowan">Ruth Mcgowan</name>
<affiliation><mods:affiliation>North Scotland Regional Genetics Service, Ashgrove House, Aberdeen, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Petit, Florence" sort="Petit, Florence" uniqKey="Petit F" first="Florence" last="Petit">Florence Petit</name>
<affiliation><mods:affiliation>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Delobel, Bruno" sort="Delobel, Bruno" uniqKey="Delobel B" first="Bruno" last="Delobel">Bruno Delobel</name>
<affiliation><mods:affiliation>Laboratoire de génétique chromosomique, Hôpital St Vincent de Paul, Lille, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Speicher, Michael R" sort="Speicher, Michael R" uniqKey="Speicher M" first="Michael R" last="Speicher">Michael R. Speicher</name>
<affiliation><mods:affiliation>Institute of Human Genetics, Medical University of Graz, Graz, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Aurora, Paul" sort="Aurora, Paul" uniqKey="Aurora P" first="Paul" last="Aurora">Paul Aurora</name>
<affiliation><mods:affiliation>Respiratory Medicine, Great Ormond Street Hospital, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kilner, David" sort="Kilner, David" uniqKey="Kilner D" first="David" last="Kilner">David Kilner</name>
<affiliation><mods:affiliation>Respiratory Medicine, Great Ormond Street Hospital, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Pellerin, Philippe" sort="Pellerin, Philippe" uniqKey="Pellerin P" first="Philippe" last="Pellerin">Philippe Pellerin</name>
<affiliation><mods:affiliation>Centre de Référence des Malformations Cranio-maxillo-faciales Rares, CHRU Lille, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Simon, Marie" sort="Simon, Marie" uniqKey="Simon M" first="Marie" last="Simon">Marie Simon</name>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Bonnefont, Jean Paul" sort="Bonnefont, Jean Paul" uniqKey="Bonnefont J" first="Jean-Paul" last="Bonnefont">Jean-Paul Bonnefont</name>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Tobias, Edward S" sort="Tobias, Edward S" uniqKey="Tobias E" first="Edward S" last="Tobias">Edward S. Tobias</name>
<affiliation><mods:affiliation>School of Medicine, University of Glasgow, Yorkhill Hospital, Glasgow, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Garcia Mi Aur, Sixto" sort="Garcia Mi Aur, Sixto" uniqKey="Garcia Mi Aur S" first="Sixto" last="García-Mi Aúr">Sixto García-Mi Aúr</name>
<affiliation><mods:affiliation>Institute for Medical and Molecular Genetics, La Paz University Hospital, Madrid, Spain</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Bitner Glindzicz, Maria" sort="Bitner Glindzicz, Maria" uniqKey="Bitner Glindzicz M" first="Maria" last="Bitner-Glindzicz">Maria Bitner-Glindzicz</name>
<affiliation><mods:affiliation>Clinical and Molecular Genetics, Institute of Child Health, UCL, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lindholm, Pernille" sort="Lindholm, Pernille" uniqKey="Lindholm P" first="Pernille" last="Lindholm">Pernille Lindholm</name>
<affiliation><mods:affiliation>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Meijer, Brigitte A" sort="Meijer, Brigitte A" uniqKey="Meijer B" first="Brigitte A" last="Meijer">Brigitte A. Meijer</name>
<affiliation><mods:affiliation>Department of Oral and Maxillofacial Surgery, Kennemer Gasthuis, Haarlem, The Netherlands</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Abadie, Veronique" sort="Abadie, Veronique" uniqKey="Abadie V" first="Véronique" last="Abadie">Véronique Abadie</name>
<affiliation><mods:affiliation>Service de Pédiatrie Générale, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Denoyelle, Francoise" sort="Denoyelle, Francoise" uniqKey="Denoyelle F" first="Françoise" last="Denoyelle">Françoise Denoyelle</name>
<affiliation><mods:affiliation>INSERM UMR-S587 and Pediatric Otolaryngology Department, Armand-Trousseau Children's Hospital, AP-HP, Paris 6 University, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Vazquez, Marie Paule" sort="Vazquez, Marie Paule" uniqKey="Vazquez M" first="Marie-Paule" last="Vazquez">Marie-Paule Vazquez</name>
<affiliation><mods:affiliation>Service de Chirurgie Maxillo-Faciale et Plastique, CRMR des Malformations de la Face et de la Cavité Buccale, Hôpital Necker-Enfants Malades, AP-HP, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Université Paris 5, UFR de Médecine Paris-Descartes, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Centre de Recherche des Cordeliers, UMR S 872, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Rotky Fast, Christa" sort="Rotky Fast, Christa" uniqKey="Rotky Fast C" first="Christa" last="Rotky-Fast">Christa Rotky-Fast</name>
<affiliation><mods:affiliation>Department of Pediatrics and Adolescence Medicine, Medical University of Graz, Graz, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Couloigner, Vincent" sort="Couloigner, Vincent" uniqKey="Couloigner V" first="Vincent" last="Couloigner">Vincent Couloigner</name>
<affiliation><mods:affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Pierrot, Sebastien" sort="Pierrot, Sebastien" uniqKey="Pierrot S" first="Sébastien" last="Pierrot">Sébastien Pierrot</name>
<affiliation><mods:affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Manach, Yves" sort="Manach, Yves" uniqKey="Manach Y" first="Yves" last="Manach">Yves Manach</name>
<affiliation><mods:affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Breton, Sylvain" sort="Breton, Sylvain" uniqKey="Breton S" first="Sylvain" last="Breton">Sylvain Breton</name>
<affiliation><mods:affiliation>AP-HP, Service d'Imagerie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Laboratoire d'Anatomie, Université Paris-Descartes, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Hendriks, Yvonne M C" sort="Hendriks, Yvonne M C" uniqKey="Hendriks Y" first="Yvonne M C" last="Hendriks">Yvonne M C. Hendriks</name>
<affiliation><mods:affiliation>Department of Clinical Genetics, Free University Medical Center, Amsterdam, The Netherlands</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Munnich, Arnold" sort="Munnich, Arnold" uniqKey="Munnich A" first="Arnold" last="Munnich">Arnold Munnich</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Jakobsen, Linda" sort="Jakobsen, Linda" uniqKey="Jakobsen L" first="Linda" last="Jakobsen">Linda Jakobsen</name>
<affiliation><mods:affiliation>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kroisel, Peter" sort="Kroisel, Peter" uniqKey="Kroisel P" first="Peter" last="Kroisel">Peter Kroisel</name>
<affiliation><mods:affiliation>Institute of Human Genetics, Medical University of Graz, Graz, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lin, Angela" sort="Lin, Angela" uniqKey="Lin A" first="Angela" last="Lin">Angela Lin</name>
<affiliation><mods:affiliation>Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kaban, Leonard B" sort="Kaban, Leonard B" uniqKey="Kaban L" first="Leonard B" last="Kaban">Leonard B. Kaban</name>
<affiliation><mods:affiliation>Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Basel Vanagaite, Lina" sort="Basel Vanagaite, Lina" uniqKey="Basel Vanagaite L" first="Lina" last="Basel-Vanagaite">Lina Basel-Vanagaite</name>
<affiliation><mods:affiliation>Pediatric Genetics, Schneider Children's Medical Center of Israel and Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Wilson, Louise" sort="Wilson, Louise" uniqKey="Wilson L" first="Louise" last="Wilson">Louise Wilson</name>
<affiliation><mods:affiliation>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Cunningham, Michael L" sort="Cunningham, Michael L" uniqKey="Cunningham M" first="Michael L" last="Cunningham">Michael L. Cunningham</name>
<affiliation><mods:affiliation>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Department of Pediatrics, University of Washington and Seattle Children's Hospital Craniofacial Center, Seattle, Washington, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lyonnet, Stanislas" sort="Lyonnet, Stanislas" uniqKey="Lyonnet S" first="Stanislas" last="Lyonnet">Stanislas Lyonnet</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Amiel, Jeanne" sort="Amiel, Jeanne" uniqKey="Amiel J" first="Jeanne" last="Amiel">Jeanne Amiel</name>
<affiliation><mods:affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</mods:affiliation>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">Journal of Medical Genetics</title>
<title level="j" type="abbrev">J Med Genet</title>
<idno type="ISSN">0022-2593</idno>
<idno type="eISSN">1468-6244</idno>
<imprint><publisher>BMJ Publishing Group Ltd</publisher>
<date type="published" when="2013-03">2013-03</date>
<biblScope unit="volume">50</biblScope>
<biblScope unit="issue">3</biblScope>
<biblScope unit="page" from="174">174</biblScope>
</imprint>
<idno type="ISSN">0022-2593</idno>
</series>
<idno type="istex">7348F3B9E6763856063CA42E9C7451B169BAE498</idno>
<idno type="DOI">10.1136/jmedgenet-2012-101331</idno>
<idno type="href">jmedgenet-50-174.pdf</idno>
<idno type="ArticleID">jmedgenet-2012-101331</idno>
<idno type="PMID">23315542</idno>
<idno type="local">jmedgenet;50/3/174</idno>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0022-2593</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass></textClass>
<langUsage><language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front><div type="abstract">Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, β 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.</div>
</front>
</TEI>
<istex><corpusName>bmj</corpusName>
<author><json:item><name>Christopher T Gordon</name>
<affiliations><json:string>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Alice Vuillot</name>
<affiliations><json:string>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Sandrine Marlin</name>
<affiliations><json:string>Centre de référence des surdités génétiques, Service de génétique médicale, Hôpital d'Enfants Armand-Trousseau AP-HP, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Erica Gerkes</name>
<affiliations><json:string>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</json:string>
</affiliations>
</json:item>
<json:item><name>Alex Henderson</name>
<affiliations><json:string>Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK</json:string>
</affiliations>
</json:item>
<json:item><name>Adila AlKindy</name>
<affiliations><json:string>Department of Genetics, Sultan Qaboos University Hospital, Muscat, Oman</json:string>
</affiliations>
</json:item>
<json:item><name>Muriel Holder-Espinasse</name>
<affiliations><json:string>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</json:string>
</affiliations>
</json:item>
<json:item><name>Sarah S Park</name>
<affiliations><json:string>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</json:string>
</affiliations>
</json:item>
<json:item><name>Asma Omarjee</name>
<affiliations><json:string>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Mateo Sanchis-Borja</name>
<affiliations><json:string>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Eya Ben Bdira</name>
<affiliations><json:string>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Myriam Oufadem</name>
<affiliations><json:string>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Birgit Sikkema-Raddatz</name>
<affiliations><json:string>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</json:string>
</affiliations>
</json:item>
<json:item><name>Alison Stewart</name>
<affiliations><json:string>West Midlands Regional Genetics Service, Birmingham, UK</json:string>
</affiliations>
</json:item>
<json:item><name>Rodger Palmer</name>
<affiliations><json:string>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</json:string>
</affiliations>
</json:item>
<json:item><name>Ruth McGowan</name>
<affiliations><json:string>North Scotland Regional Genetics Service, Ashgrove House, Aberdeen, UK</json:string>
</affiliations>
</json:item>
<json:item><name>Florence Petit</name>
<affiliations><json:string>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</json:string>
</affiliations>
</json:item>
<json:item><name>Bruno Delobel</name>
<affiliations><json:string>Laboratoire de génétique chromosomique, Hôpital St Vincent de Paul, Lille, France</json:string>
</affiliations>
</json:item>
<json:item><name>Michael R Speicher</name>
<affiliations><json:string>Institute of Human Genetics, Medical University of Graz, Graz, Austria</json:string>
</affiliations>
</json:item>
<json:item><name>Paul Aurora</name>
<affiliations><json:string>Respiratory Medicine, Great Ormond Street Hospital, London, UK</json:string>
</affiliations>
</json:item>
<json:item><name>David Kilner</name>
<affiliations><json:string>Respiratory Medicine, Great Ormond Street Hospital, London, UK</json:string>
</affiliations>
</json:item>
<json:item><name>Philippe Pellerin</name>
<affiliations><json:string>Centre de Référence des Malformations Cranio-maxillo-faciales Rares, CHRU Lille, France</json:string>
</affiliations>
</json:item>
<json:item><name>Marie Simon</name>
<affiliations><json:string>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Jean-Paul Bonnefont</name>
<affiliations><json:string>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Edward S Tobias</name>
<affiliations><json:string>School of Medicine, University of Glasgow, Yorkhill Hospital, Glasgow, UK</json:string>
</affiliations>
</json:item>
<json:item><name>Sixto García-Miñaúr</name>
<affiliations><json:string>Institute for Medical and Molecular Genetics, La Paz University Hospital, Madrid, Spain</json:string>
</affiliations>
</json:item>
<json:item><name>Maria Bitner-Glindzicz</name>
<affiliations><json:string>Clinical and Molecular Genetics, Institute of Child Health, UCL, London, UK</json:string>
</affiliations>
</json:item>
<json:item><name>Pernille Lindholm</name>
<affiliations><json:string>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</json:string>
</affiliations>
</json:item>
<json:item><name>Brigitte A Meijer</name>
<affiliations><json:string>Department of Oral and Maxillofacial Surgery, Kennemer Gasthuis, Haarlem, The Netherlands</json:string>
</affiliations>
</json:item>
<json:item><name>Véronique Abadie</name>
<affiliations><json:string>Service de Pédiatrie Générale, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Françoise Denoyelle</name>
<affiliations><json:string>INSERM UMR-S587 and Pediatric Otolaryngology Department, Armand-Trousseau Children's Hospital, AP-HP, Paris 6 University, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Marie-Paule Vazquez</name>
<affiliations><json:string>Service de Chirurgie Maxillo-Faciale et Plastique, CRMR des Malformations de la Face et de la Cavité Buccale, Hôpital Necker-Enfants Malades, AP-HP, Paris, France</json:string>
<json:string>Université Paris 5, UFR de Médecine Paris-Descartes, Paris, France</json:string>
<json:string>Centre de Recherche des Cordeliers, UMR S 872, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Christa Rotky-Fast</name>
<affiliations><json:string>Department of Pediatrics and Adolescence Medicine, Medical University of Graz, Graz, Austria</json:string>
</affiliations>
</json:item>
<json:item><name>Vincent Couloigner</name>
<affiliations><json:string>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Sébastien Pierrot</name>
<affiliations><json:string>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Yves Manach</name>
<affiliations><json:string>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Sylvain Breton</name>
<affiliations><json:string>AP-HP, Service d'Imagerie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France</json:string>
<json:string>Laboratoire d'Anatomie, Université Paris-Descartes, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Yvonne M C Hendriks</name>
<affiliations><json:string>Department of Clinical Genetics, Free University Medical Center, Amsterdam, The Netherlands</json:string>
</affiliations>
</json:item>
<json:item><name>Arnold Munnich</name>
<affiliations><json:string>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</json:string>
<json:string>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Linda Jakobsen</name>
<affiliations><json:string>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</json:string>
</affiliations>
</json:item>
<json:item><name>Peter Kroisel</name>
<affiliations><json:string>Institute of Human Genetics, Medical University of Graz, Graz, Austria</json:string>
</affiliations>
</json:item>
<json:item><name>Angela Lin</name>
<affiliations><json:string>Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts, USA</json:string>
</affiliations>
</json:item>
<json:item><name>Leonard B Kaban</name>
<affiliations><json:string>Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA</json:string>
</affiliations>
</json:item>
<json:item><name>Lina Basel-Vanagaite</name>
<affiliations><json:string>Pediatric Genetics, Schneider Children's Medical Center of Israel and Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel</json:string>
<json:string>Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;</json:string>
<json:string>Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel</json:string>
</affiliations>
</json:item>
<json:item><name>Louise Wilson</name>
<affiliations><json:string>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</json:string>
</affiliations>
</json:item>
<json:item><name>Michael L Cunningham</name>
<affiliations><json:string>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</json:string>
<json:string>Department of Pediatrics, University of Washington and Seattle Children's Hospital Craniofacial Center, Seattle, Washington, USA</json:string>
</affiliations>
</json:item>
<json:item><name>Stanislas Lyonnet</name>
<affiliations><json:string>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</json:string>
<json:string>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</json:string>
</affiliations>
</json:item>
<json:item><name>Jeanne Amiel</name>
<affiliations><json:string>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</json:string>
<json:string>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</json:string>
</affiliations>
</json:item>
</author>
<subject><json:item><lang><json:string>eng</json:string>
</lang>
<value>PLCB4</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>GNAI3</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>auriculocondylar syndrome</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>question mark ear</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>micrognathia</value>
</json:item>
</subject>
<articleId><json:string>jmedgenet-2012-101331</json:string>
</articleId>
<language><json:string>eng</json:string>
</language>
<originalGenre><json:string>research-article</json:string>
</originalGenre>
<abstract>Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, β 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.</abstract>
<qualityIndicators><score>9.88</score>
<pdfVersion>1.3</pdfVersion>
<pdfPageSize>595.276 x 793.701 pts</pdfPageSize>
<refBibsNative>true</refBibsNative>
<keywordCount>5</keywordCount>
<abstractCharCount>1700</abstractCharCount>
<pdfWordCount>8602</pdfWordCount>
<pdfCharCount>55682</pdfCharCount>
<pdfPageCount>13</pdfPageCount>
<abstractWordCount>240</abstractWordCount>
</qualityIndicators>
<title>Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome</title>
<pmid><json:string>23315542</json:string>
</pmid>
<refBibs><json:item><author><json:item><name>NM Kokitsu-Nakata</name>
</json:item>
<json:item><name>RM Zechi-Ceide</name>
</json:item>
<json:item><name>S Vendramini-Pittoli</name>
</json:item>
<json:item><name>VL Romanelli Tavares</name>
</json:item>
<json:item><name>MR Passos-Bueno</name>
</json:item>
<json:item><name>ML Guion-Almeida</name>
</json:item>
</author>
<host><volume>158A</volume>
<pages><last>65</last>
<first>59</first>
</pages>
<author></author>
<title>Am J Med Genet A</title>
</host>
<title>Auriculo-condylar syndrome. Confronting a diagnostic challenge</title>
</json:item>
<json:item><author><json:item><name>C Masotti</name>
</json:item>
<json:item><name>KG Oliveira</name>
</json:item>
<json:item><name>F Poerner</name>
</json:item>
<json:item><name>A Splendore</name>
</json:item>
<json:item><name>J Souza</name>
</json:item>
<json:item><name>S Freitas Rda</name>
</json:item>
<json:item><name>R Zechi-Ceide</name>
</json:item>
<json:item><name>ML Guion-Almeida</name>
</json:item>
<json:item><name>MR Passos-Bueno</name>
</json:item>
</author>
<host><volume>16</volume>
<author></author>
<title>Eur J Hum Genet</title>
</host>
<title>Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity</title>
</json:item>
<json:item><author><json:item><name>AL Storm</name>
</json:item>
<json:item><name>JM Johnson</name>
</json:item>
<json:item><name>E Lammer</name>
</json:item>
<json:item><name>GE Green</name>
</json:item>
<json:item><name>C Cunniff</name>
</json:item>
</author>
<host><volume>138A</volume>
<author></author>
<title>Am J Med Genet A</title>
</host>
<title>Auriculo-condylar syndrome is associated with highly variable ear and mandibular defects in multiple kindreds</title>
</json:item>
<json:item><author><json:item><name>S Ozturk</name>
</json:item>
<json:item><name>M Sengezer</name>
</json:item>
<json:item><name>S Isik</name>
</json:item>
<json:item><name>D Gul</name>
</json:item>
<json:item><name>F Zor</name>
</json:item>
</author>
<host><volume>16</volume>
<author></author>
<title>J Craniofac Surg</title>
</host>
<title>The correction of auricular and mandibular deformities in auriculo-condylar syndrome</title>
</json:item>
<json:item><author><json:item><name>ML Guion-Almeida</name>
</json:item>
<json:item><name>RM Zechi-Ceide</name>
</json:item>
<json:item><name>S Vendramini</name>
</json:item>
<json:item><name>NM Kokitsu-Nakata</name>
</json:item>
</author>
<host><volume>112</volume>
<author></author>
<title>Am J Med Genet</title>
</host>
<title>Auriculo-condylar syndrome: additional patients</title>
</json:item>
<json:item><author><json:item><name>MT Divizia</name>
</json:item>
<json:item><name>A Cordone</name>
</json:item>
<json:item><name>M Bado</name>
</json:item>
<json:item><name>L Rosaia</name>
</json:item>
<json:item><name>M Cirillo Silengo</name>
</json:item>
<json:item><name>R Ravazzolo</name>
</json:item>
<json:item><name>M Lerone</name>
</json:item>
</author>
<host><volume>11</volume>
<author></author>
<title>Clin Dysmorphol</title>
</host>
<title>Auriculo-condylar syndrome or new syndrome?</title>
</json:item>
<json:item><author><json:item><name>M Priolo</name>
</json:item>
<json:item><name>M Lerone</name>
</json:item>
<json:item><name>L Rosaia</name>
</json:item>
<json:item><name>EP Calcagno</name>
</json:item>
<json:item><name>AK Sadeghi</name>
</json:item>
<json:item><name>F Ghezzi</name>
</json:item>
<json:item><name>R Ravazzolo</name>
</json:item>
<json:item><name>M Silengo</name>
</json:item>
</author>
<host><volume>9</volume>
<author></author>
<title>Clin Dysmorphol</title>
</host>
<title>Question mark ears, temporo-mandibular joint malformation and hypotonia: auriculo-condylar syndrome or a distinct entity?</title>
</json:item>
<json:item><author><json:item><name>ML Guion-Almeida</name>
</json:item>
<json:item><name>NM Kokitsu-Nakata</name>
</json:item>
<json:item><name>RM Zechi-Ceide</name>
</json:item>
<json:item><name>S Vendramini</name>
</json:item>
</author>
<host><volume>86</volume>
<author></author>
<title>Am J Med Genet</title>
</host>
<title>Auriculo-condylar syndrome: further evidence for a new disorder</title>
</json:item>
<json:item><author><json:item><name>EH Gerkes</name>
</json:item>
<json:item><name>CM van Ravenswaaij</name>
</json:item>
<json:item><name>AJ van Essen</name>
</json:item>
</author>
<host><volume>51</volume>
<author></author>
<title>Eur J Med Genet</title>
</host>
<title>Question mark ears and post-auricular tags</title>
</json:item>
<json:item><author><json:item><name>MM Al-Qattan</name>
</json:item>
</author>
<host><volume>102</volume>
<author></author>
<title>Plast Reconstr Surg</title>
</host>
<title>Cosman (question mark) ear: congenital auricular cleft between the fifth and sixth hillocks</title>
</json:item>
<json:item><author><json:item><name>T Takato</name>
</json:item>
<json:item><name>H Takeda</name>
</json:item>
<json:item><name>M Kamei</name>
</json:item>
<json:item><name>K Uchiyama</name>
</json:item>
</author>
<host><volume>22</volume>
<pages><last>73</last>
<first>69</first>
</pages>
<author></author>
<title>Ann Plast Surg</title>
</host>
<title>The question mark ear (congenital auricular cleft): a familial case</title>
</json:item>
<json:item><author><json:item><name>M Fumiiri</name>
</json:item>
<json:item><name>H Hyakusoku</name>
</json:item>
</author>
<host><volume>71</volume>
<author></author>
<title>Plast Reconstr Surg</title>
</host>
<title>Congenital auricular cleft</title>
</json:item>
<json:item><author><json:item><name>V Uuspaa</name>
</json:item>
</author>
<host><volume>12</volume>
<author></author>
<title>Scand J Plast Reconstr Surg</title>
</host>
<title>Combined bilateral external ear deformity and hypoplastic mandible. Case report</title>
</json:item>
<json:item><author><json:item><name>M Jampol</name>
</json:item>
<json:item><name>G Repetto</name>
</json:item>
<json:item><name>DA Keith</name>
</json:item>
<json:item><name>H Curtin</name>
</json:item>
<json:item><name>J Remensynder</name>
</json:item>
<json:item><name>LB Holmes</name>
</json:item>
</author>
<host><volume>75</volume>
<author></author>
<title>Am J Med Genet</title>
</host>
<title>New syndrome? Prominent, constricted ears with malformed condyle of the mandible</title>
</json:item>
<json:item><author><json:item><name>MS Erlich</name>
</json:item>
<json:item><name>ML Cunningham</name>
</json:item>
<json:item><name>L Hudgins</name>
</json:item>
</author>
<host><volume>95</volume>
<author></author>
<title>Am J Med Genet</title>
</host>
<title>Transmission of the dysgnathia complex from mother to daughter</title>
</json:item>
<json:item><author><json:item><name>CM Posso</name>
</json:item>
<json:item><name>GA Wolff</name>
</json:item>
<json:item><name>LD Suarez</name>
</json:item>
</author>
<host><volume>35</volume>
<author></author>
<title>Aesthetic Plast Surg</title>
</host>
<title>Question mark ear deformity: a combined method for correction</title>
</json:item>
<json:item><author><json:item><name>B Pan</name>
</json:item>
<json:item><name>H Jiang</name>
</json:item>
<json:item><name>Y Zhao</name>
</json:item>
<json:item><name>L Lin</name>
</json:item>
<json:item><name>D Guo</name>
</json:item>
<json:item><name>H Zhuang</name>
</json:item>
</author>
<host><volume>63</volume>
<pages><last>35</last>
<first>28</first>
</pages>
<author></author>
<title>J Plast Reconstr Aesthet Surg</title>
</host>
<title>Clinical analysis, repair and aetiology of question mark ear</title>
</json:item>
<json:item><author><json:item><name>V Shkalim</name>
</json:item>
<json:item><name>N Eliaz</name>
</json:item>
<json:item><name>N Linder</name>
</json:item>
<json:item><name>P Merlob</name>
</json:item>
<json:item><name>L Basel-Vanagaite</name>
</json:item>
</author>
<host><volume>146A</volume>
<author></author>
<title>Am J Med Genet A</title>
</host>
<title>Autosomal dominant isolated question mark ear</title>
</json:item>
<json:item><author><json:item><name>H Vayvada</name>
</json:item>
<json:item><name>C Karaca</name>
</json:item>
<json:item><name>A Menderes</name>
</json:item>
<json:item><name>M Yilmaz</name>
</json:item>
</author>
<host><volume>29</volume>
<author></author>
<title>Aesthetic Plast Surg</title>
</host>
<title>Question mark ear deformity and a modified surgical correction method: a case report</title>
</json:item>
<json:item><author><json:item><name>S Brodovsky</name>
</json:item>
<json:item><name>M Westreich</name>
</json:item>
</author>
<host><volume>100</volume>
<author></author>
<title>Plast Reconstr Surg</title>
</host>
<title>Question mark ear: a method for repair</title>
</json:item>
<json:item><author><json:item><name>B Cosman</name>
</json:item>
<json:item><name>H Bellin</name>
</json:item>
<json:item><name>GF Crikelair</name>
</json:item>
</author>
<host><volume>46</volume>
<author></author>
<title>Plast Reconstr Surg</title>
</host>
<title>The Question Mark ear</title>
</json:item>
<json:item><author><json:item><name>PA Baker</name>
</json:item>
<json:item><name>S Aftimos</name>
</json:item>
<json:item><name>BJ Anderson</name>
</json:item>
</author>
<host><volume>14</volume>
<author></author>
<title>Paediatr Anaesth</title>
</host>
<title>Airway management during an EXIT procedure for a fetus with dysgnathia complex</title>
</json:item>
<json:item><author><json:item><name>AV Greig</name>
</json:item>
<json:item><name>S Podda</name>
</json:item>
<json:item><name>CH Thorne</name>
</json:item>
<json:item><name>JG McCarthy</name>
</json:item>
</author>
<host><volume>129</volume>
<author></author>
<title>Plast Reconstr Surg</title>
</host>
<title>The question mark ear in patients with mandibular hypoplasia</title>
</json:item>
<json:item><author><json:item><name>MJ Rieder</name>
</json:item>
<json:item><name>GE Green</name>
</json:item>
<json:item><name>SS Park</name>
</json:item>
<json:item><name>BD Stamper</name>
</json:item>
<json:item><name>CT Gordon</name>
</json:item>
<json:item><name>JM Johnson</name>
</json:item>
<json:item><name>CM Cunniff</name>
</json:item>
<json:item><name>JD Smith</name>
</json:item>
<json:item><name>SB Emery</name>
</json:item>
<json:item><name>S Lyonnet</name>
</json:item>
<json:item><name>J Amiel</name>
</json:item>
<json:item><name>M Holder</name>
</json:item>
<json:item><name>AA Heggie</name>
</json:item>
<json:item><name>MJ Bamshad</name>
</json:item>
<json:item><name>DA Nickerson</name>
</json:item>
<json:item><name>TC Cox</name>
</json:item>
<json:item><name>AV Hing</name>
</json:item>
<json:item><name>JA Horst</name>
</json:item>
<json:item><name>ML Cunningham</name>
</json:item>
</author>
<host><volume>90</volume>
<author></author>
<title>Am J Hum Genet</title>
</host>
<title>A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome</title>
</json:item>
<json:item><author><json:item><name>MJ Stuffken</name>
</json:item>
<json:item><name>DB Tuinzing</name>
</json:item>
</author>
<host><volume>115</volume>
<author></author>
<title>Ned Tijdschr Tandheelkd</title>
</host>
<title>Dysgnathia complex, a rare deviation</title>
</json:item>
<json:item><author><json:item><name>RW Vincent</name>
</json:item>
<json:item><name>RF Ryan</name>
</json:item>
<json:item><name>CG Longenecker</name>
</json:item>
</author>
<host><volume>28</volume>
<author></author>
<title>Plast Reconstr Surg Transplant Bull</title>
</host>
<title>Malformation of ear associated with urogenital anomalies</title>
</json:item>
<json:item><author><json:item><name>C Park</name>
</json:item>
</author>
<host><volume>101</volume>
<author></author>
<title>Plast Reconstr Surg</title>
</host>
<title>Correction of the unilateral question mark ear</title>
</json:item>
<json:item><author><json:item><name>DE Clouthier</name>
</json:item>
<json:item><name>E Garcia</name>
</json:item>
<json:item><name>TF Schilling</name>
</json:item>
</author>
<host><volume>152A</volume>
<author></author>
<title>Am J Med Genet A</title>
</host>
<title>Regulation of facial morphogenesis by endothelin signaling: insights from mice and fish</title>
</json:item>
<json:item><author><json:item><name>MB Walker</name>
</json:item>
<json:item><name>CT Miller</name>
</json:item>
<json:item><name>ME Swartz</name>
</json:item>
<json:item><name>JK Eberhart</name>
</json:item>
<json:item><name>CB Kimmel</name>
</json:item>
</author>
<host><volume>304</volume>
<pages><last>207</last>
<first>194</first>
</pages>
<author></author>
<title>Dev Biol</title>
</host>
<title>Phospholipase C, beta 3 is required for Endothelin1 regulation of pharyngeal arch patterning in zebrafish</title>
</json:item>
<json:item><author><json:item><name>R McGowan</name>
</json:item>
<json:item><name>V Murday</name>
</json:item>
<json:item><name>E Kinning</name>
</json:item>
<json:item><name>S Garcia</name>
</json:item>
<json:item><name>D Koppel</name>
</json:item>
<json:item><name>M Whiteford</name>
</json:item>
</author>
<host><volume>20</volume>
<pages><last>10</last>
<first>1</first>
</pages>
<author></author>
<title>Clin Dysmorphol</title>
</host>
<title>Novel features in auriculo-condylar syndrome</title>
</json:item>
<json:item><author><json:item><name>M Soundararajan</name>
</json:item>
<json:item><name>FS Willard</name>
</json:item>
<json:item><name>AJ Kimple</name>
</json:item>
<json:item><name>AP Turnbull</name>
</json:item>
<json:item><name>LJ Ball</name>
</json:item>
<json:item><name>GA Schoch</name>
</json:item>
<json:item><name>C Gileadi</name>
</json:item>
<json:item><name>OY Fedorov</name>
</json:item>
<json:item><name>EF Dowler</name>
</json:item>
<json:item><name>VA Higman</name>
</json:item>
<json:item><name>SQ Hutsell</name>
</json:item>
<json:item><name>M Sundstrom</name>
</json:item>
<json:item><name>DA Doyle</name>
</json:item>
<json:item><name>DP Siderovski</name>
</json:item>
</author>
<host><volume>105</volume>
<author></author>
<title>Proc Natl Acad Sci USA</title>
</host>
<title>Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits</title>
</json:item>
<json:item><author><json:item><name>GL Waldo</name>
</json:item>
<json:item><name>TK Ricks</name>
</json:item>
<json:item><name>SN Hicks</name>
</json:item>
<json:item><name>ML Cheever</name>
</json:item>
<json:item><name>T Kawano</name>
</json:item>
<json:item><name>K Tsuboi</name>
</json:item>
<json:item><name>X Wang</name>
</json:item>
<json:item><name>C Montell</name>
</json:item>
<json:item><name>T Kozasa</name>
</json:item>
<json:item><name>J Sondek</name>
</json:item>
<json:item><name>TK Harden</name>
</json:item>
</author>
<host><volume>330</volume>
<author></author>
<title>Science</title>
</host>
<title>Kinetic scaffolding mediated by a phospholipase C-beta and Gq signaling complex</title>
</json:item>
<json:item><author><json:item><name>A Hunter</name>
</json:item>
<json:item><name>JL Frias</name>
</json:item>
<json:item><name>G Gillessen-Kaesbach</name>
</json:item>
<json:item><name>H Hughes</name>
</json:item>
<json:item><name>KL Jones</name>
</json:item>
<json:item><name>L Wilson</name>
</json:item>
</author>
<host><volume>149A</volume>
<pages><last>60</last>
<first>40</first>
</pages>
<author></author>
<title>Am J Med Genet A</title>
</host>
<title>Elements of morphology: standard terminology for the ear</title>
</json:item>
<json:item><author><json:item><name>DF Conrad</name>
</json:item>
<json:item><name>C Bird</name>
</json:item>
<json:item><name>B Blackburne</name>
</json:item>
<json:item><name>S Lindsay</name>
</json:item>
<json:item><name>L Mamanova</name>
</json:item>
<json:item><name>C Lee</name>
</json:item>
<json:item><name>DJ Turner</name>
</json:item>
<json:item><name>ME Hurles</name>
</json:item>
</author>
<host><volume>42</volume>
<author></author>
<title>Nat Genet</title>
</host>
<title>Mutation spectrum revealed by breakpoint sequencing of human germline CNVs</title>
</json:item>
<json:item><author><json:item><name>DA Dettlaff-Swiercz</name>
</json:item>
<json:item><name>N Wettschureck</name>
</json:item>
<json:item><name>A Moers</name>
</json:item>
<json:item><name>K Huber</name>
</json:item>
<json:item><name>S Offermanns</name>
</json:item>
</author>
<host><volume>282</volume>
<author></author>
<title>Dev Biol</title>
</host>
<title>Characteristic defects in neural crest cell-specific Galphaq/Galpha11- and Galpha12/Galpha13-deficient mice</title>
</json:item>
<json:item><author><json:item><name>K Ivey</name>
</json:item>
<json:item><name>B Tyson</name>
</json:item>
<json:item><name>P Ukidwe</name>
</json:item>
<json:item><name>DG McFadden</name>
</json:item>
<json:item><name>G Levi</name>
</json:item>
<json:item><name>EN Olson</name>
</json:item>
<json:item><name>D Srivastava</name>
</json:item>
<json:item><name>TM Wilkie</name>
</json:item>
</author>
<host><volume>255</volume>
<author></author>
<title>Dev Biol</title>
</host>
<title>Galphaq and Galpha11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme</title>
</json:item>
<json:item><author><json:item><name>S Offermanns</name>
</json:item>
<json:item><name>LP Zhao</name>
</json:item>
<json:item><name>A Gohla</name>
</json:item>
<json:item><name>I Sarosi</name>
</json:item>
<json:item><name>MI Simon</name>
</json:item>
<json:item><name>TM Wilkie</name>
</json:item>
</author>
<host><volume>17</volume>
<author></author>
<title>EMBO J</title>
</host>
<title>Embryonic cardiomyocyte hypoplasia and craniofacial defects in G alpha q/G alpha 11-mutant mice</title>
</json:item>
<json:item><author><json:item><name>T Sato</name>
</json:item>
<json:item><name>Y Kawamura</name>
</json:item>
<json:item><name>R Asai</name>
</json:item>
<json:item><name>T Amano</name>
</json:item>
<json:item><name>Y Uchijima</name>
</json:item>
<json:item><name>DA Dettlaff-Swiercz</name>
</json:item>
<json:item><name>S Offermanns</name>
</json:item>
<json:item><name>Y Kurihara</name>
</json:item>
<json:item><name>H Kurihara</name>
</json:item>
</author>
<host><volume>135</volume>
<author></author>
<title>Development</title>
</host>
<title>Recombinase-mediated cassette exchange reveals the selective use of Gq/G11-dependent and -independent endothelin 1/endothelin type A receptor signaling in pharyngeal arch development</title>
</json:item>
<json:item><author><json:item><name>L Birnbaumer</name>
</json:item>
<json:item><name>AR Zurita</name>
</json:item>
</author>
<host><volume>30</volume>
<author></author>
<title>J Recept Signal Transduct Res</title>
</host>
<title>On the roles of Mg in the activation of G proteins</title>
</json:item>
<json:item><author><json:item><name>MM Nezarati</name>
</json:item>
<json:item><name>S Aftimos</name>
</json:item>
</author>
<host><volume>16</volume>
<pages><last>13</last>
<first>9</first>
</pages>
<author></author>
<title>Clin Dysmorphol</title>
</host>
<title>Microtia, severe micrognathia and absent ossicles: auriculo-condylar syndrome or new entity?</title>
</json:item>
<json:item><author><json:item><name>C Gaultier</name>
</json:item>
<json:item><name>J Amiel</name>
</json:item>
<json:item><name>S Dauger</name>
</json:item>
<json:item><name>H Trang</name>
</json:item>
<json:item><name>S Lyonnet</name>
</json:item>
<json:item><name>J Gallego</name>
</json:item>
<json:item><name>M Simonneau</name>
</json:item>
</author>
<host><volume>55</volume>
<author></author>
<title>Pediatr Res</title>
</host>
<title>Genetics and early disturbances of breathing control</title>
</json:item>
<json:item><author><json:item><name>K Nagano</name>
</json:item>
<json:item><name>K Fukami</name>
</json:item>
<json:item><name>T Minagawa</name>
</json:item>
<json:item><name>Y Watanabe</name>
</json:item>
<json:item><name>C Ozaki</name>
</json:item>
<json:item><name>T Takenawa</name>
</json:item>
</author>
<host><volume>274</volume>
<author></author>
<title>J Biol Chem</title>
</host>
<title>A novel phospholipase C delta4 (PLCdelta4) splice variant as a negative regulator of PLC</title>
</json:item>
<json:item><author><json:item><name>SR Lalani</name>
</json:item>
<json:item><name>JV Thakuria</name>
</json:item>
<json:item><name>GF Cox</name>
</json:item>
<json:item><name>X Wang</name>
</json:item>
<json:item><name>W Bi</name>
</json:item>
<json:item><name>MS Bray</name>
</json:item>
<json:item><name>C Shaw</name>
</json:item>
<json:item><name>SW Cheung</name>
</json:item>
<json:item><name>AC Chinault</name>
</json:item>
<json:item><name>BA Boggs</name>
</json:item>
<json:item><name>Z Ou</name>
</json:item>
<json:item><name>EK Brundage</name>
</json:item>
<json:item><name>JR Lupski</name>
</json:item>
<json:item><name>J Gentile</name>
</json:item>
<json:item><name>S Waisbren</name>
</json:item>
<json:item><name>A Pursley</name>
</json:item>
<json:item><name>L Ma</name>
</json:item>
<json:item><name>M Khajavi</name>
</json:item>
<json:item><name>G Zapata</name>
</json:item>
<json:item><name>R Friedman</name>
</json:item>
<json:item><name>JJ Kim</name>
</json:item>
<json:item><name>JA Towbin</name>
</json:item>
<json:item><name>P Stankiewicz</name>
</json:item>
<json:item><name>S Schnittger</name>
</json:item>
<json:item><name>I Hansmann</name>
</json:item>
<json:item><name>T Ai</name>
</json:item>
<json:item><name>S Sood</name>
</json:item>
<json:item><name>XH Wehrens</name>
</json:item>
<json:item><name>JF Martin</name>
</json:item>
<json:item><name>JW Belmont</name>
</json:item>
<json:item><name>L Potocki</name>
</json:item>
</author>
<host><volume>46</volume>
<author></author>
<title>J Med Genet</title>
</host>
<title>20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable neurocognitive deficits</title>
</json:item>
<json:item><author><json:item><name>F Anad</name>
</json:item>
<json:item><name>J Burn</name>
</json:item>
<json:item><name>D Matthews</name>
</json:item>
<json:item><name>I Cross</name>
</json:item>
<json:item><name>BC Davison</name>
</json:item>
<json:item><name>R Mueller</name>
</json:item>
<json:item><name>M Sands</name>
</json:item>
<json:item><name>DM Lillington</name>
</json:item>
<json:item><name>E Eastham</name>
</json:item>
</author>
<host><volume>27</volume>
<author></author>
<title>J Med Genet</title>
</host>
<title>Alagille syndrome and deletion of 20p</title>
</json:item>
<json:item><author><json:item><name>M Shohat</name>
</json:item>
<json:item><name>V Herman</name>
</json:item>
<json:item><name>S Melmed</name>
</json:item>
<json:item><name>N Neufeld</name>
</json:item>
<json:item><name>R Schreck</name>
</json:item>
<json:item><name>S Pulst</name>
</json:item>
<json:item><name>JM Graham Jr</name>
</json:item>
<json:item><name>DL Rimoin</name>
</json:item>
<json:item><name>JR Korenberg</name>
</json:item>
</author>
<host><volume>39</volume>
<pages><last>63</last>
<first>56</first>
</pages>
<author></author>
<title>Am J Med Genet</title>
</host>
<title>Deletion of 20p 11.23––pter with normal growth hormone-releasing hormone genes</title>
</json:item>
<json:item><author><json:item><name>ML Robert</name>
</json:item>
<json:item><name>T Lopez</name>
</json:item>
<json:item><name>J Crolla</name>
</json:item>
<json:item><name>S Huang</name>
</json:item>
<json:item><name>C Owen</name>
</json:item>
<json:item><name>L Burvill-Holmes</name>
</json:item>
<json:item><name>O Stumper</name>
</json:item>
<json:item><name>PD Turnpenny</name>
</json:item>
</author>
<host><volume>16</volume>
<author></author>
<title>Clin Dysmorphol</title>
</host>
<title>Alagille syndrome with deletion 20p12.2-p12.3 and hypoplastic left heart</title>
</json:item>
<json:item><author><json:item><name>BM Kamath</name>
</json:item>
<json:item><name>BD Thiel</name>
</json:item>
<json:item><name>X Gai</name>
</json:item>
<json:item><name>LK Conlin</name>
</json:item>
<json:item><name>PS Munoz</name>
</json:item>
<json:item><name>J Glessner</name>
</json:item>
<json:item><name>D Clark</name>
</json:item>
<json:item><name>DM Warthen</name>
</json:item>
<json:item><name>TH Shaikh</name>
</json:item>
<json:item><name>E Mihci</name>
</json:item>
<json:item><name>DA Piccoli</name>
</json:item>
<json:item><name>SF Grant</name>
</json:item>
<json:item><name>H Hakonarson</name>
</json:item>
<json:item><name>ID Krantz</name>
</json:item>
<json:item><name>NB Spinner</name>
</json:item>
</author>
<host><volume>30</volume>
<author></author>
<title>Hum Mutat</title>
</host>
<title>SNP array mapping of chromosome 20p deletions: genotypes, phenotypes, and copy number variation</title>
</json:item>
<json:item><author><json:item><name>L Le Gloan</name>
</json:item>
<json:item><name>O Pichon</name>
</json:item>
<json:item><name>B Isidor</name>
</json:item>
<json:item><name>M Boceno</name>
</json:item>
<json:item><name>JM Rival</name>
</json:item>
<json:item><name>A David</name>
</json:item>
<json:item><name>C Le Caignec</name>
</json:item>
</author>
<host><volume>51</volume>
<author></author>
<title>Eur J Med Genet</title>
</host>
<title>A 8.26Mb deletion in 6q16 and a 4.95Mb deletion in 20p12 including JAG1 and BMP2 in a patient with Alagille syndrome and Wolff-Parkinson-White syndrome</title>
</json:item>
<json:item><author><json:item><name>E Cheong</name>
</json:item>
<json:item><name>Y Zheng</name>
</json:item>
<json:item><name>K Lee</name>
</json:item>
<json:item><name>J Lee</name>
</json:item>
<json:item><name>S Kim</name>
</json:item>
<json:item><name>M Sanati</name>
</json:item>
<json:item><name>S Lee</name>
</json:item>
<json:item><name>YS Kim</name>
</json:item>
<json:item><name>HS Shin</name>
</json:item>
</author>
<host><volume>106</volume>
<author></author>
<title>Proc Natl Acad Sci USA</title>
</host>
<title>Deletion of phospholipase C beta4 in thalamocortical relay nucleus leads to absence seizures</title>
</json:item>
<json:item><author><json:item><name>H Jiang</name>
</json:item>
<json:item><name>A Lyubarsky</name>
</json:item>
<json:item><name>R Dodd</name>
</json:item>
<json:item><name>N Vardi</name>
</json:item>
<json:item><name>E Pugh</name>
</json:item>
<json:item><name>D Baylor</name>
</json:item>
<json:item><name>MI Simon</name>
</json:item>
<json:item><name>D Wu</name>
</json:item>
</author>
<host><volume>93</volume>
<author></author>
<title>Proc Natl Acad Sci USA</title>
</host>
<title>Phospholipase C beta 4 is involved in modulating the visual response in mice</title>
</json:item>
<json:item><author><json:item><name>M Kano</name>
</json:item>
<json:item><name>K Hashimoto</name>
</json:item>
<json:item><name>M Watanabe</name>
</json:item>
<json:item><name>H Kurihara</name>
</json:item>
<json:item><name>S Offermanns</name>
</json:item>
<json:item><name>H Jiang</name>
</json:item>
<json:item><name>Y Wu</name>
</json:item>
<json:item><name>K Jun</name>
</json:item>
<json:item><name>HS Shin</name>
</json:item>
<json:item><name>Y Inoue</name>
</json:item>
<json:item><name>MI Simon</name>
</json:item>
<json:item><name>D Wu</name>
</json:item>
</author>
<host><volume>95</volume>
<author></author>
<title>Proc Natl Acad Sci USA</title>
</host>
<title>Phospholipase cbeta4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum</title>
</json:item>
<json:item><author><json:item><name>D Kim</name>
</json:item>
<json:item><name>KS Jun</name>
</json:item>
<json:item><name>SB Lee</name>
</json:item>
<json:item><name>NG Kang</name>
</json:item>
<json:item><name>DS Min</name>
</json:item>
<json:item><name>YH Kim</name>
</json:item>
<json:item><name>SH Ryu</name>
</json:item>
<json:item><name>PG Suh</name>
</json:item>
<json:item><name>HS Shin</name>
</json:item>
</author>
<host><volume>389</volume>
<author></author>
<title>Nature</title>
</host>
<title>Phospholipase C isozymes selectively couple to specific neurotransmitter receptors</title>
</json:item>
<json:item><author><json:item><name>T Xue</name>
</json:item>
<json:item><name>MT Do</name>
</json:item>
<json:item><name>A Riccio</name>
</json:item>
<json:item><name>Z Jiang</name>
</json:item>
<json:item><name>J Hsieh</name>
</json:item>
<json:item><name>HC Wang</name>
</json:item>
<json:item><name>SL Merbs</name>
</json:item>
<json:item><name>DS Welsbie</name>
</json:item>
<json:item><name>T Yoshioka</name>
</json:item>
<json:item><name>P Weissgerber</name>
</json:item>
<json:item><name>S Stolz</name>
</json:item>
<json:item><name>V Flockerzi</name>
</json:item>
<json:item><name>M Freichel</name>
</json:item>
<json:item><name>MI Simon</name>
</json:item>
<json:item><name>DE Clapham</name>
</json:item>
<json:item><name>KW Yau</name>
</json:item>
</author>
<host><volume>479</volume>
<pages><last>73</last>
<first>67</first>
</pages>
<author></author>
<title>Nature</title>
</host>
<title>Melanopsin signalling in mammalian iris and retina</title>
</json:item>
<json:item><author><json:item><name>M Ikeda</name>
</json:item>
<json:item><name>M Hirono</name>
</json:item>
<json:item><name>T Sugiyama</name>
</json:item>
<json:item><name>T Moriya</name>
</json:item>
<json:item><name>M Ikeda-Sagara</name>
</json:item>
<json:item><name>N Eguchi</name>
</json:item>
<json:item><name>Y Urade</name>
</json:item>
<json:item><name>T Yoshioka</name>
</json:item>
</author>
<host><volume>4</volume>
<pages><first>7737</first>
</pages>
<author></author>
<title>PLoS One</title>
</host>
<title>Phospholipase C-beta4 is essential for the progression of the normal sleep sequence and ultradian body temperature rhythms in mice</title>
</json:item>
<json:item><author><json:item><name>J Shin</name>
</json:item>
<json:item><name>G Gireesh</name>
</json:item>
<json:item><name>SW Kim</name>
</json:item>
<json:item><name>DS Kim</name>
</json:item>
<json:item><name>S Lee</name>
</json:item>
<json:item><name>YS Kim</name>
</json:item>
<json:item><name>M Watanabe</name>
</json:item>
<json:item><name>HS Shin</name>
</json:item>
</author>
<host><volume>29</volume>
<author></author>
<title>J Neurosci</title>
</host>
<title>Phospholipase C beta 4 in the medial septum controls cholinergic theta oscillations and anxiety behaviors</title>
</json:item>
<json:item><author><json:item><name>S Lee</name>
</json:item>
<json:item><name>T Ahmed</name>
</json:item>
<json:item><name>H Kim</name>
</json:item>
<json:item><name>S Choi</name>
</json:item>
<json:item><name>DS Kim</name>
</json:item>
<json:item><name>SJ Kim</name>
</json:item>
<json:item><name>J Cho</name>
</json:item>
<json:item><name>HS Shin</name>
</json:item>
</author>
<host><volume>15</volume>
<author></author>
<title>Nat Neurosci</title>
</host>
<title>Bidirectional modulation of fear extinction by mediodorsal thalamic firing in mice</title>
</json:item>
<json:item><author><json:item><name>K Wennerberg</name>
</json:item>
<json:item><name>KL Rossman</name>
</json:item>
<json:item><name>CJ Der</name>
</json:item>
</author>
<host><volume>118</volume>
<author></author>
<title>J Cell Sci</title>
</host>
<title>The Ras superfamily at a glance</title>
</json:item>
<json:item><author><json:item><name>LA Feig</name>
</json:item>
<json:item><name>GM Cooper</name>
</json:item>
</author>
<host><volume>8</volume>
<author></author>
<title>Mol Cell Biol</title>
</host>
<title>Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP</title>
</json:item>
<json:item><author><json:item><name>LA Feig</name>
</json:item>
</author>
<host><volume>1</volume>
<pages><last>7</last>
<first>25</first>
</pages>
<author></author>
<title>Nat Cell Biol</title>
</host>
<title>Tools of the trade: use of dominant-inhibitory mutants of Ras-family GTPases</title>
</json:item>
<json:item><author><json:item><name>B Barren</name>
</json:item>
<json:item><name>NO Artemyev</name>
</json:item>
</author>
<host><volume>85</volume>
<author></author>
<title>J Neurosci Res</title>
</host>
<title>Mechanisms of dominant negative G-protein alpha subunits</title>
</json:item>
<json:item><author><json:item><name>JG Dauwerse</name>
</json:item>
<json:item><name>J Dixon</name>
</json:item>
<json:item><name>S Seland</name>
</json:item>
<json:item><name>CA Ruivenkamp</name>
</json:item>
<json:item><name>A van Haeringen</name>
</json:item>
<json:item><name>LH Hoefsloot</name>
</json:item>
<json:item><name>DJ Peters</name>
</json:item>
<json:item><name>AC Boers</name>
</json:item>
<json:item><name>C Daumer-Haas</name>
</json:item>
<json:item><name>R Maiwald</name>
</json:item>
<json:item><name>C Zweier</name>
</json:item>
<json:item><name>B Kerr</name>
</json:item>
<json:item><name>AM Cobo</name>
</json:item>
<json:item><name>JF Toral</name>
</json:item>
<json:item><name>AJ Hoogeboom</name>
</json:item>
<json:item><name>DR Lohmann</name>
</json:item>
<json:item><name>U Hehr</name>
</json:item>
<json:item><name>MJ Dixon</name>
</json:item>
<json:item><name>MH Breuning</name>
</json:item>
<json:item><name>D Wieczorek</name>
</json:item>
</author>
<host><volume>43</volume>
<author></author>
<title>Nat Genet</title>
</host>
<title>Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome</title>
</json:item>
<json:item><author><json:item><name>JF Cote</name>
</json:item>
<json:item><name>K Vuori</name>
</json:item>
</author>
<host><volume>17</volume>
<author></author>
<title>Trends Cell Biol</title>
</host>
<title>GEF what? Dock180 and related proteins help Rac to polarize cells in new ways</title>
</json:item>
<json:item><author><json:item><name>R Shaheen</name>
</json:item>
<json:item><name>E Faqeih</name>
</json:item>
<json:item><name>A Sunker</name>
</json:item>
<json:item><name>H Morsy</name>
</json:item>
<json:item><name>T Al-Sheddi</name>
</json:item>
<json:item><name>HE Shamseldin</name>
</json:item>
<json:item><name>N Adly</name>
</json:item>
<json:item><name>M Hashem</name>
</json:item>
<json:item><name>FS Alkuraya</name>
</json:item>
</author>
<host><volume>89</volume>
<author></author>
<title>Am J Hum Genet</title>
</host>
<title>Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-Oliver syndrome</title>
</json:item>
<json:item><author><json:item><name>SA Yatsenko</name>
</json:item>
<json:item><name>MC Kruer</name>
</json:item>
<json:item><name>PI Bader</name>
</json:item>
<json:item><name>D Corzo</name>
</json:item>
<json:item><name>J Schuette</name>
</json:item>
<json:item><name>CE Keegan</name>
</json:item>
<json:item><name>B Nowakowska</name>
</json:item>
<json:item><name>S Peacock</name>
</json:item>
<json:item><name>WW Cai</name>
</json:item>
<json:item><name>DA Peiffer</name>
</json:item>
<json:item><name>KL Gunderson</name>
</json:item>
<json:item><name>Z Ou</name>
</json:item>
<json:item><name>AC Chinault</name>
</json:item>
<json:item><name>SW Cheung</name>
</json:item>
</author>
<host><volume>76</volume>
<pages><last>62</last>
<first>54</first>
</pages>
<author></author>
<title>Clin Genet</title>
</host>
<title>Identification of critical regions for clinical features of distal 10q deletion syndrome</title>
</json:item>
<json:item><author><json:item><name>MR Passos-Bueno</name>
</json:item>
<json:item><name>CC Ornelas</name>
</json:item>
<json:item><name>RD Fanganiello</name>
</json:item>
</author>
<host><volume>149A</volume>
<author></author>
<title>Am J Med Genet A</title>
</host>
<title>Syndromes of the first and second pharyngeal arches: A review</title>
</json:item>
</refBibs>
<genre><json:string>research-article</json:string>
</genre>
<host><volume>50</volume>
<publisherId><json:string>jmg</json:string>
</publisherId>
<pages><first>174</first>
</pages>
<issn><json:string>0022-2593</json:string>
</issn>
<issue>3</issue>
<genre><json:string>journal</json:string>
</genre>
<language><json:string>unknown</json:string>
</language>
<eissn><json:string>1468-6244</json:string>
</eissn>
<title>Journal of Medical Genetics</title>
</host>
<categories><wos><json:string>science</json:string>
<json:string>genetics & heredity</json:string>
</wos>
<scienceMetrix><json:string>health sciences</json:string>
<json:string>biomedical research</json:string>
<json:string>genetics & heredity</json:string>
</scienceMetrix>
</categories>
<publicationDate>2013</publicationDate>
<copyrightDate>2013</copyrightDate>
<doi><json:string>10.1136/jmedgenet-2012-101331</json:string>
</doi>
<id>7348F3B9E6763856063CA42E9C7451B169BAE498</id>
<score>0.17209098</score>
<fulltext><json:item><extension>pdf</extension>
<original>true</original>
<mimetype>application/pdf</mimetype>
<uri>https://api.istex.fr/document/7348F3B9E6763856063CA42E9C7451B169BAE498/fulltext/pdf</uri>
</json:item>
<json:item><extension>zip</extension>
<original>false</original>
<mimetype>application/zip</mimetype>
<uri>https://api.istex.fr/document/7348F3B9E6763856063CA42E9C7451B169BAE498/fulltext/zip</uri>
</json:item>
<istex:fulltextTEI uri="https://api.istex.fr/document/7348F3B9E6763856063CA42E9C7451B169BAE498/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome</title>
</titleStmt>
<publicationStmt><authority>ISTEX</authority>
<publisher>BMJ Publishing Group Ltd</publisher>
<availability><p>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</p>
</availability>
<date>2013-01-12</date>
</publicationStmt>
<notesStmt><note> CTG and AV contributed equally</note>
</notesStmt>
<sourceDesc><biblStruct type="inbook"><analytic><title level="a">Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome</title>
<author xml:id="author-1"><persName><forename type="first">Christopher T</forename>
<surname>Gordon</surname>
</persName>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
</author>
<author xml:id="author-2"><persName><forename type="first">Alice</forename>
<surname>Vuillot</surname>
</persName>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
</author>
<author xml:id="author-3"><persName><forename type="first">Sandrine</forename>
<surname>Marlin</surname>
</persName>
<affiliation>Centre de référence des surdités génétiques, Service de génétique médicale, Hôpital d'Enfants Armand-Trousseau AP-HP, Paris, France</affiliation>
</author>
<author xml:id="author-4"><persName><forename type="first">Erica</forename>
<surname>Gerkes</surname>
</persName>
<affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</affiliation>
</author>
<author xml:id="author-5"><persName><forename type="first">Alex</forename>
<surname>Henderson</surname>
</persName>
<affiliation>Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK</affiliation>
</author>
<author xml:id="author-6"><persName><forename type="first">Adila</forename>
<surname>AlKindy</surname>
</persName>
<affiliation>Department of Genetics, Sultan Qaboos University Hospital, Muscat, Oman</affiliation>
</author>
<author xml:id="author-7"><persName><forename type="first">Muriel</forename>
<surname>Holder-Espinasse</surname>
</persName>
<affiliation>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</affiliation>
</author>
<author xml:id="author-8"><persName><forename type="first">Sarah S</forename>
<surname>Park</surname>
</persName>
<affiliation>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</affiliation>
</author>
<author xml:id="author-9"><persName><forename type="first">Asma</forename>
<surname>Omarjee</surname>
</persName>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
</author>
<author xml:id="author-10"><persName><forename type="first">Mateo</forename>
<surname>Sanchis-Borja</surname>
</persName>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
</author>
<author xml:id="author-11"><persName><forename type="first">Eya Ben</forename>
<surname>Bdira</surname>
</persName>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
</author>
<author xml:id="author-12"><persName><forename type="first">Myriam</forename>
<surname>Oufadem</surname>
</persName>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
</author>
<author xml:id="author-13"><persName><forename type="first">Birgit</forename>
<surname>Sikkema-Raddatz</surname>
</persName>
<affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</affiliation>
</author>
<author xml:id="author-14"><persName><forename type="first">Alison</forename>
<surname>Stewart</surname>
</persName>
<affiliation>West Midlands Regional Genetics Service, Birmingham, UK</affiliation>
</author>
<author xml:id="author-15"><persName><forename type="first">Rodger</forename>
<surname>Palmer</surname>
</persName>
<affiliation>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</affiliation>
</author>
<author xml:id="author-16"><persName><forename type="first">Ruth</forename>
<surname>McGowan</surname>
</persName>
<affiliation>North Scotland Regional Genetics Service, Ashgrove House, Aberdeen, UK</affiliation>
</author>
<author xml:id="author-17"><persName><forename type="first">Florence</forename>
<surname>Petit</surname>
</persName>
<affiliation>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</affiliation>
</author>
<author xml:id="author-18"><persName><forename type="first">Bruno</forename>
<surname>Delobel</surname>
</persName>
<affiliation>Laboratoire de génétique chromosomique, Hôpital St Vincent de Paul, Lille, France</affiliation>
</author>
<author xml:id="author-19"><persName><forename type="first">Michael R</forename>
<surname>Speicher</surname>
</persName>
<affiliation>Institute of Human Genetics, Medical University of Graz, Graz, Austria</affiliation>
</author>
<author xml:id="author-20"><persName><forename type="first">Paul</forename>
<surname>Aurora</surname>
</persName>
<affiliation>Respiratory Medicine, Great Ormond Street Hospital, London, UK</affiliation>
</author>
<author xml:id="author-21"><persName><forename type="first">David</forename>
<surname>Kilner</surname>
</persName>
<affiliation>Respiratory Medicine, Great Ormond Street Hospital, London, UK</affiliation>
</author>
<author xml:id="author-22"><persName><forename type="first">Philippe</forename>
<surname>Pellerin</surname>
</persName>
<affiliation>Centre de Référence des Malformations Cranio-maxillo-faciales Rares, CHRU Lille, France</affiliation>
</author>
<author xml:id="author-23"><persName><forename type="first">Marie</forename>
<surname>Simon</surname>
</persName>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
</author>
<author xml:id="author-24"><persName><forename type="first">Jean-Paul</forename>
<surname>Bonnefont</surname>
</persName>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
</author>
<author xml:id="author-25"><persName><forename type="first">Edward S</forename>
<surname>Tobias</surname>
</persName>
<affiliation>School of Medicine, University of Glasgow, Yorkhill Hospital, Glasgow, UK</affiliation>
</author>
<author xml:id="author-26"><persName><forename type="first">Sixto</forename>
<surname>García-Miñaúr</surname>
</persName>
<affiliation>Institute for Medical and Molecular Genetics, La Paz University Hospital, Madrid, Spain</affiliation>
</author>
<author xml:id="author-27"><persName><forename type="first">Maria</forename>
<surname>Bitner-Glindzicz</surname>
</persName>
<affiliation>Clinical and Molecular Genetics, Institute of Child Health, UCL, London, UK</affiliation>
</author>
<author xml:id="author-28"><persName><forename type="first">Pernille</forename>
<surname>Lindholm</surname>
</persName>
<affiliation>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</affiliation>
</author>
<author xml:id="author-29"><persName><forename type="first">Brigitte A</forename>
<surname>Meijer</surname>
</persName>
<affiliation>Department of Oral and Maxillofacial Surgery, Kennemer Gasthuis, Haarlem, The Netherlands</affiliation>
</author>
<author xml:id="author-30"><persName><forename type="first">Véronique</forename>
<surname>Abadie</surname>
</persName>
<affiliation>Service de Pédiatrie Générale, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
</author>
<author xml:id="author-31"><persName><forename type="first">Françoise</forename>
<surname>Denoyelle</surname>
</persName>
<affiliation>INSERM UMR-S587 and Pediatric Otolaryngology Department, Armand-Trousseau Children's Hospital, AP-HP, Paris 6 University, Paris, France</affiliation>
</author>
<author xml:id="author-32"><persName><forename type="first">Marie-Paule</forename>
<surname>Vazquez</surname>
</persName>
<affiliation>Service de Chirurgie Maxillo-Faciale et Plastique, CRMR des Malformations de la Face et de la Cavité Buccale, Hôpital Necker-Enfants Malades, AP-HP, Paris, France</affiliation>
<affiliation>Université Paris 5, UFR de Médecine Paris-Descartes, Paris, France</affiliation>
<affiliation>Centre de Recherche des Cordeliers, UMR S 872, Paris, France</affiliation>
</author>
<author xml:id="author-33"><persName><forename type="first">Christa</forename>
<surname>Rotky-Fast</surname>
</persName>
<affiliation>Department of Pediatrics and Adolescence Medicine, Medical University of Graz, Graz, Austria</affiliation>
</author>
<author xml:id="author-34"><persName><forename type="first">Vincent</forename>
<surname>Couloigner</surname>
</persName>
<affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</affiliation>
</author>
<author xml:id="author-35"><persName><forename type="first">Sébastien</forename>
<surname>Pierrot</surname>
</persName>
<affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</affiliation>
</author>
<author xml:id="author-36"><persName><forename type="first">Yves</forename>
<surname>Manach</surname>
</persName>
<affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</affiliation>
</author>
<author xml:id="author-37"><persName><forename type="first">Sylvain</forename>
<surname>Breton</surname>
</persName>
<affiliation>AP-HP, Service d'Imagerie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
<affiliation>Laboratoire d'Anatomie, Université Paris-Descartes, Paris, France</affiliation>
</author>
<author xml:id="author-38"><persName><forename type="first">Yvonne M C</forename>
<surname>Hendriks</surname>
</persName>
<affiliation>Department of Clinical Genetics, Free University Medical Center, Amsterdam, The Netherlands</affiliation>
</author>
<author xml:id="author-39"><persName><forename type="first">Arnold</forename>
<surname>Munnich</surname>
</persName>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
</author>
<author xml:id="author-40"><persName><forename type="first">Linda</forename>
<surname>Jakobsen</surname>
</persName>
<affiliation>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</affiliation>
</author>
<author xml:id="author-41"><persName><forename type="first">Peter</forename>
<surname>Kroisel</surname>
</persName>
<affiliation>Institute of Human Genetics, Medical University of Graz, Graz, Austria</affiliation>
</author>
<author xml:id="author-42"><persName><forename type="first">Angela</forename>
<surname>Lin</surname>
</persName>
<affiliation>Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts, USA</affiliation>
</author>
<author xml:id="author-43"><persName><forename type="first">Leonard B</forename>
<surname>Kaban</surname>
</persName>
<affiliation>Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA</affiliation>
</author>
<author xml:id="author-44"><persName><forename type="first">Lina</forename>
<surname>Basel-Vanagaite</surname>
</persName>
<affiliation>Pediatric Genetics, Schneider Children's Medical Center of Israel and Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel</affiliation>
<affiliation>Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;</affiliation>
<affiliation>Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel</affiliation>
</author>
<author xml:id="author-45"><persName><forename type="first">Louise</forename>
<surname>Wilson</surname>
</persName>
<affiliation>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</affiliation>
</author>
<author xml:id="author-46"><persName><forename type="first">Michael L</forename>
<surname>Cunningham</surname>
</persName>
<affiliation>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</affiliation>
<affiliation>Department of Pediatrics, University of Washington and Seattle Children's Hospital Craniofacial Center, Seattle, Washington, USA</affiliation>
</author>
<author xml:id="author-47"><persName><forename type="first">Stanislas</forename>
<surname>Lyonnet</surname>
</persName>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
</author>
<author xml:id="author-48"><persName><forename type="first">Jeanne</forename>
<surname>Amiel</surname>
</persName>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
</author>
</analytic>
<monogr><title level="j">Journal of Medical Genetics</title>
<title level="j" type="abbrev">J Med Genet</title>
<idno type="pISSN">0022-2593</idno>
<idno type="eISSN">1468-6244</idno>
<imprint><publisher>BMJ Publishing Group Ltd</publisher>
<date type="published" when="2013-03"></date>
<biblScope unit="volume">50</biblScope>
<biblScope unit="issue">3</biblScope>
<biblScope unit="page" from="174">174</biblScope>
</imprint>
</monogr>
<idno type="istex">7348F3B9E6763856063CA42E9C7451B169BAE498</idno>
<idno type="DOI">10.1136/jmedgenet-2012-101331</idno>
<idno type="href">jmedgenet-50-174.pdf</idno>
<idno type="ArticleID">jmedgenet-2012-101331</idno>
<idno type="PMID">23315542</idno>
<idno type="local">jmedgenet;50/3/174</idno>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><creation><date>2013-01-12</date>
</creation>
<langUsage><language ident="en">en</language>
</langUsage>
<abstract><p>Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, β 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.</p>
</abstract>
<textClass><keywords scheme="keyword"><list><head>keywords</head>
<item><term>PLCB4</term>
</item>
<item><term>GNAI3</term>
</item>
<item><term>auriculocondylar syndrome</term>
</item>
<item><term>question mark ear</term>
</item>
<item><term>micrognathia</term>
</item>
</list>
</keywords>
</textClass>
</profileDesc>
<revisionDesc><change when="2013-01-12">Created</change>
<change when="2013-03">Published</change>
</revisionDesc>
</teiHeader>
</istex:fulltextTEI>
<json:item><extension>txt</extension>
<original>false</original>
<mimetype>text/plain</mimetype>
<uri>https://api.istex.fr/document/7348F3B9E6763856063CA42E9C7451B169BAE498/fulltext/txt</uri>
</json:item>
</fulltext>
<metadata><istex:metadataXml wicri:clean="corpus bmj" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="no"</istex:xmlDeclaration>
<istex:docType PUBLIC="-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" URI="archivearticle.dtd" name="istex:docType"></istex:docType>
<istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">jmedgenet</journal-id>
<journal-id journal-id-type="nlm-ta">J Med Genet</journal-id>
<journal-id journal-id-type="publisher-id">jmg</journal-id>
<journal-title>Journal of Medical Genetics</journal-title>
<abbrev-journal-title abbrev-type="publisher">J Med Genet</abbrev-journal-title>
<abbrev-journal-title>J Med Genet</abbrev-journal-title>
<issn pub-type="ppub">0022-2593</issn>
<issn pub-type="epub">1468-6244</issn>
<publisher><publisher-name>BMJ Publishing Group Ltd</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="publisher-id">jmedgenet-2012-101331</article-id>
<article-id pub-id-type="doi">10.1136/jmedgenet-2012-101331</article-id>
<article-id pub-id-type="other">jmedgenet;50/3/174</article-id>
<article-id pub-id-type="other">jmedgenet;jmedgenet-2012-101331</article-id>
<article-id pub-id-type="pmid">23315542</article-id>
<article-id pub-id-type="other">174</article-id>
<article-id pub-id-type="other">jmedgenet-2012-101331</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Developmental defects</subject>
</subj-group>
<series-title>Original article</series-title>
</article-categories>
<title-group><article-title>Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Gordon</surname>
<given-names>Christopher T</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vuillot</surname>
<given-names>Alice</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Marlin</surname>
<given-names>Sandrine</given-names>
</name>
<xref ref-type="aff" rid="af2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gerkes</surname>
<given-names>Erica</given-names>
</name>
<xref ref-type="aff" rid="af3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Henderson</surname>
<given-names>Alex</given-names>
</name>
<xref ref-type="aff" rid="af4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>AlKindy</surname>
<given-names>Adila</given-names>
</name>
<xref ref-type="aff" rid="af5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Holder-Espinasse</surname>
<given-names>Muriel</given-names>
</name>
<xref ref-type="aff" rid="af6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Park</surname>
<given-names>Sarah S</given-names>
</name>
<xref ref-type="aff" rid="af7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Omarjee</surname>
<given-names>Asma</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sanchis-Borja</surname>
<given-names>Mateo</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bdira</surname>
<given-names>Eya Ben</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Oufadem</surname>
<given-names>Myriam</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sikkema-Raddatz</surname>
<given-names>Birgit</given-names>
</name>
<xref ref-type="aff" rid="af3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Stewart</surname>
<given-names>Alison</given-names>
</name>
<xref ref-type="aff" rid="af8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Palmer</surname>
<given-names>Rodger</given-names>
</name>
<xref ref-type="aff" rid="af9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McGowan</surname>
<given-names>Ruth</given-names>
</name>
<xref ref-type="aff" rid="af10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Petit</surname>
<given-names>Florence</given-names>
</name>
<xref ref-type="aff" rid="af6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Delobel</surname>
<given-names>Bruno</given-names>
</name>
<xref ref-type="aff" rid="af11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Speicher</surname>
<given-names>Michael R</given-names>
</name>
<xref ref-type="aff" rid="af12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Aurora</surname>
<given-names>Paul</given-names>
</name>
<xref ref-type="aff" rid="af13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kilner</surname>
<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="af13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pellerin</surname>
<given-names>Philippe</given-names>
</name>
<xref ref-type="aff" rid="af14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Simon</surname>
<given-names>Marie</given-names>
</name>
<xref ref-type="aff" rid="af15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bonnefont</surname>
<given-names>Jean-Paul</given-names>
</name>
<xref ref-type="aff" rid="af15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tobias</surname>
<given-names>Edward S</given-names>
</name>
<xref ref-type="aff" rid="af16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>García-Miñaúr</surname>
<given-names>Sixto</given-names>
</name>
<xref ref-type="aff" rid="af17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bitner-Glindzicz</surname>
<given-names>Maria</given-names>
</name>
<xref ref-type="aff" rid="af18">18</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lindholm</surname>
<given-names>Pernille</given-names>
</name>
<xref ref-type="aff" rid="af19">19</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Meijer</surname>
<given-names>Brigitte A</given-names>
</name>
<xref ref-type="aff" rid="af20">20</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Abadie</surname>
<given-names>Véronique</given-names>
</name>
<xref ref-type="aff" rid="af21">21</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Denoyelle</surname>
<given-names>Françoise</given-names>
</name>
<xref ref-type="aff" rid="af22">22</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vazquez</surname>
<given-names>Marie-Paule</given-names>
</name>
<xref ref-type="aff" rid="af23">23</xref>
<xref ref-type="aff" rid="af24">24</xref>
<xref ref-type="aff" rid="af25">25</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rotky-Fast</surname>
<given-names>Christa</given-names>
</name>
<xref ref-type="aff" rid="af26">26</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Couloigner</surname>
<given-names>Vincent</given-names>
</name>
<xref ref-type="aff" rid="af27">27</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pierrot</surname>
<given-names>Sébastien</given-names>
</name>
<xref ref-type="aff" rid="af27">27</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Manach</surname>
<given-names>Yves</given-names>
</name>
<xref ref-type="aff" rid="af27">27</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Breton</surname>
<given-names>Sylvain</given-names>
</name>
<xref ref-type="aff" rid="af28">28</xref>
<xref ref-type="aff" rid="af29">29</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hendriks</surname>
<given-names>Yvonne M C</given-names>
</name>
<xref ref-type="aff" rid="af30">30</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Munnich</surname>
<given-names>Arnold</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jakobsen</surname>
<given-names>Linda</given-names>
</name>
<xref ref-type="aff" rid="af19">19</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kroisel</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="af12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lin</surname>
<given-names>Angela</given-names>
</name>
<xref ref-type="aff" rid="af31">31</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kaban</surname>
<given-names>Leonard B</given-names>
</name>
<xref ref-type="aff" rid="af32">32</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Basel-Vanagaite</surname>
<given-names>Lina</given-names>
</name>
<xref ref-type="aff" rid="af33">33</xref>
<xref ref-type="aff" rid="af34">34</xref>
<xref ref-type="aff" rid="af35">35</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wilson</surname>
<given-names>Louise</given-names>
</name>
<xref ref-type="aff" rid="af9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cunningham</surname>
<given-names>Michael L</given-names>
</name>
<xref ref-type="aff" rid="af7">7</xref>
<xref ref-type="aff" rid="af36">36</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lyonnet</surname>
<given-names>Stanislas</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Amiel</surname>
<given-names>Jeanne</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
<xref ref-type="aff" rid="af15">15</xref>
</contrib>
</contrib-group>
<aff id="af1"><label>1</label>
<addr-line>INSERM U781</addr-line>
, <institution>Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine</institution>
, <addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af2"><label>2</label>
<institution>Centre de référence des surdités génétiques</institution>
, <institution>Service de génétique médicale, Hôpital d'Enfants Armand-Trousseau AP-HP</institution>
, <addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af3"><label>3</label>
<addr-line>Department of Genetics</addr-line>
, <institution>University of Groningen, University Medical Center Groningen</institution>
, <addr-line>Groningen</addr-line>
, <country>the Netherlands</country>
</aff>
<aff id="af4"><label>4</label>
<addr-line>Northern Genetics Service</addr-line>
, <institution>Newcastle upon Tyne Hospitals NHS Foundation Trust</institution>
, <addr-line>Newcastle Upon Tyne</addr-line>
, <country>UK</country>
</aff>
<aff id="af5"><label>5</label>
<addr-line>Department of Genetics</addr-line>
, <institution>Sultan Qaboos University Hospital</institution>
, <addr-line>Muscat</addr-line>
, <country>Oman</country>
</aff>
<aff id="af6"><label>6</label>
<addr-line>Service de Génétique Clinique</addr-line>
, <institution>Hôpital Jeanne de Flandre</institution>
, <addr-line>CHRU Lille</addr-line>
, <country>France</country>
</aff>
<aff id="af7"><label>7</label>
<addr-line>Center for Tissue and Cell Sciences</addr-line>
, <institution>Seattle Children's Research Institute</institution>
, <addr-line>Seattle</addr-line>
, <country>USA</country>
</aff>
<aff id="af8"><label>8</label>
<addr-line>West Midlands Regional Genetics Service, Birmingham</addr-line>
, <country>UK</country>
</aff>
<aff id="af9"><label>9</label>
<addr-line>North East Thames Regional Genetics Service</addr-line>
, <institution>Great Ormond Street Hospital</institution>
, <addr-line>London</addr-line>
, <country>UK</country>
</aff>
<aff id="af10"><label>10</label>
<addr-line>North Scotland Regional Genetics Service</addr-line>
, <institution>Ashgrove House</institution>
, <addr-line>Aberdeen</addr-line>
, <country>UK</country>
</aff>
<aff id="af11"><label>11</label>
<addr-line>Laboratoire de génétique chromosomique</addr-line>
, <institution>Hôpital St Vincent de Paul</institution>
, <addr-line>Lille</addr-line>
, <country>France</country>
</aff>
<aff id="af12"><label>12</label>
<institution>Institute of Human Genetics</institution>
, <institution>Medical University of Graz</institution>
, <addr-line>Graz</addr-line>
, <country>Austria</country>
</aff>
<aff id="af13"><label>13</label>
<addr-line>Respiratory Medicine</addr-line>
, <institution>Great Ormond Street Hospital</institution>
, <addr-line>London</addr-line>
, <country>UK</country>
</aff>
<aff id="af14"><label>14</label>
<institution>Centre de Référence des Malformations Cranio-maxillo-faciales Rares</institution>
, <addr-line>CHRU Lille</addr-line>
, <country>France</country>
</aff>
<aff id="af15"><label>15</label>
<addr-line>AP-HP, Département de Génétique</addr-line>
, <institution>Hôpital Necker-Enfants Malades</institution>
, <addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af16"><label>16</label>
<institution>School of Medicine</institution>
, <institution>University of Glasgow, Yorkhill Hospital</institution>
, <addr-line>Glasgow</addr-line>
, <country>UK</country>
</aff>
<aff id="af17"><label>17</label>
<institution>Institute for Medical and Molecular Genetics, La Paz University Hospital</institution>
, <addr-line>Madrid</addr-line>
, <country>Spain</country>
</aff>
<aff id="af18"><label>18</label>
<addr-line>Clinical and Molecular Genetics</addr-line>
, <institution>Institute of Child Health, UCL</institution>
, <addr-line>London</addr-line>
, <country>UK</country>
</aff>
<aff id="af19"><label>19</label>
<addr-line>Department of Plastic and Reconstructive Surgery</addr-line>
, <institution>Copenhagen University Hospital</institution>
, <addr-line>Rigshospitalet</addr-line>
, <country>Denmark</country>
</aff>
<aff id="af20"><label>20</label>
<addr-line>Department of Oral and Maxillofacial Surgery</addr-line>
, <institution>Kennemer Gasthuis</institution>
, <addr-line>Haarlem</addr-line>
, <country>The Netherlands</country>
</aff>
<aff id="af21"><label>21</label>
<addr-line>Service de Pédiatrie Générale</addr-line>
, <institution>Université Paris Descartes</institution>
, <institution>Hôpital Necker-Enfants Malades</institution>
, <addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af22"><label>22</label>
<addr-line>INSERM UMR-S587 and Pediatric Otolaryngology Department</addr-line>
, <institution>Armand-Trousseau Children's Hospital, AP-HP, Paris 6 University</institution>
, <addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af23"><label>23</label>
<addr-line>Service de Chirurgie Maxillo-Faciale et Plastique</addr-line>
, <institution>CRMR des Malformations de la Face et de la Cavité Buccale, Hôpital Necker-Enfants Malades, AP-HP,</institution>
<addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af24"><label>24</label>
Université Paris 5, UFR de Médecine Paris-Descartes, Paris, France</aff>
<aff id="af25"><label>25</label>
<institution>Centre de Recherche des Cordeliers, UMR S 872</institution>
, <addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af26"><label>26</label>
<addr-line>Department of Pediatrics and Adolescence Medicine</addr-line>
, <institution>Medical University of Graz</institution>
, <addr-line>Graz</addr-line>
, <country>Austria</country>
</aff>
<aff id="af27"><label>27</label>
<addr-line>Service d'ORL Pediatrique</addr-line>
, <institution>Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5</institution>
, <addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af28"><label>28</label>
<addr-line>AP-HP, Service d'Imagerie Pédiatrique</addr-line>
, <institution>Hôpital Necker-Enfants Malades</institution>
, <addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af29"><label>29</label>
<addr-line>Laboratoire d'Anatomie</addr-line>
, <institution>Université Paris-Descartes</institution>
, <addr-line>Paris</addr-line>
, <country>France</country>
</aff>
<aff id="af30"><label>30</label>
<addr-line>Department of Clinical Genetics</addr-line>
, <institution>Free University Medical Center</institution>
, <addr-line>Amsterdam</addr-line>
, <country>The Netherlands</country>
</aff>
<aff id="af31"><label>31</label>
<addr-line>Genetics Unit</addr-line>
, <institution>MassGeneral Hospital for Children</institution>
, <addr-line>Boston, Massachusetts</addr-line>
, <country>USA</country>
</aff>
<aff id="af32"><label>32</label>
<addr-line>Department of Oral and Maxillofacial Surgery</addr-line>
, <institution>Massachusetts General Hospital</institution>
, <addr-line>Boston, Massachusetts</addr-line>
, <country>USA</country>
</aff>
<aff id="af33"><label>33</label>
Pediatric Genetics, Schneider Children's Medical Center of Israel and Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel</aff>
<aff id="af34"><label>34</label>
<addr-line>Sackler Faculty of Medicine</addr-line>
, <institution>Tel Aviv University</institution>
, <addr-line>Tel Aviv</addr-line>
, <country>Israel</country>
;</aff>
<aff id="af35"><label>35</label>
<addr-line>Felsenstein Medical Research Center</addr-line>
, <institution>Rabin Medical Center</institution>
, <addr-line>Petah Tikva</addr-line>
, <country>Israel</country>
</aff>
<aff id="af36"><label>36</label>
<addr-line>Department of Pediatrics</addr-line>
, <institution>University of Washington and Seattle Children's Hospital Craniofacial Center</institution>
, <addr-line>Seattle</addr-line>
, Washington, <country>USA</country>
</aff>
<author-notes><corresp><label>Correspondence to</label>
Dr Christopher T Gordon and Professor Jeanne Amiel, INSERM U781, Tour Lavoisier 2ème étage, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, Paris 75015, France; <email>chris.gordon@inserm.fr</email>
, <email>jeanne.amiel@inserm.fr</email>
</corresp>
<fn><p> CTG and AV contributed equally</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>3</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub-original"><day>12</day>
<month>1</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>12</day>
<month>1</month>
<year>2013</year>
</pub-date>
<volume>50</volume>
<volume-id pub-id-type="other">50</volume-id>
<volume-id pub-id-type="other">50</volume-id>
<issue>3</issue>
<issue-id pub-id-type="other">jmedgenet;50/3</issue-id>
<issue-id pub-id-type="other">3</issue-id>
<issue-id pub-id-type="other">50/3</issue-id>
<fpage>174</fpage>
<history><date date-type="received"><day>1</day>
<month>10</month>
<year>2012</year>
</date>
<date date-type="rev-recd"><day>6</day>
<month>12</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>7</day>
<month>12</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<self-uri content-type="pdf" xlink:role="full-text" xlink:href="jmedgenet-50-174.pdf"></self-uri>
<abstract><sec><title>Background</title>
<p>Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, β 4 (<italic>PLCB4</italic>
) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (<italic>GNAI3</italic>
) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development.</p>
</sec>
<sec><title>Results</title>
<p>We report eight additional cases ascribed to <italic>PLCB4</italic>
or <italic>GNAI3</italic>
gene lesions, comprising six heterozygous <italic>PLCB4</italic>
missense mutations, one heterozygous <italic>GNAI3</italic>
missense mutation and one homozygous <italic>PLCB4</italic>
intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS <italic>PLCB4</italic>
missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous <italic>PLCB4</italic>
deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by <italic>PLCB4</italic>
haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients.</p>
</sec>
<sec><title>Conclusions</title>
<p>These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the <italic>PLCB4</italic>
gene lesion.</p>
</sec>
</abstract>
<kwd-group><kwd>PLCB4</kwd>
<kwd>GNAI3</kwd>
<kwd>auriculocondylar syndrome</kwd>
<kwd>question mark ear</kwd>
<kwd>micrognathia</kwd>
</kwd-group>
</article-meta>
</front>
</article>
</istex:document>
</istex:metadataXml>
<mods version="3.6"><titleInfo><title>Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome</title>
<partName>Original article</partName>
</titleInfo>
<titleInfo type="alternative" contentType="CDATA"><title>Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome</title>
<partName>Original article</partName>
</titleInfo>
<name type="personal"><namePart type="given">Christopher T</namePart>
<namePart type="family">Gordon</namePart>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Alice</namePart>
<namePart type="family">Vuillot</namePart>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Sandrine</namePart>
<namePart type="family">Marlin</namePart>
<affiliation>Centre de référence des surdités génétiques, Service de génétique médicale, Hôpital d'Enfants Armand-Trousseau AP-HP, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Erica</namePart>
<namePart type="family">Gerkes</namePart>
<affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Alex</namePart>
<namePart type="family">Henderson</namePart>
<affiliation>Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Adila</namePart>
<namePart type="family">AlKindy</namePart>
<affiliation>Department of Genetics, Sultan Qaboos University Hospital, Muscat, Oman</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Muriel</namePart>
<namePart type="family">Holder-Espinasse</namePart>
<affiliation>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Sarah S</namePart>
<namePart type="family">Park</namePart>
<affiliation>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Asma</namePart>
<namePart type="family">Omarjee</namePart>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Mateo</namePart>
<namePart type="family">Sanchis-Borja</namePart>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Eya Ben</namePart>
<namePart type="family">Bdira</namePart>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Myriam</namePart>
<namePart type="family">Oufadem</namePart>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Birgit</namePart>
<namePart type="family">Sikkema-Raddatz</namePart>
<affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Alison</namePart>
<namePart type="family">Stewart</namePart>
<affiliation>West Midlands Regional Genetics Service, Birmingham, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Rodger</namePart>
<namePart type="family">Palmer</namePart>
<affiliation>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Ruth</namePart>
<namePart type="family">McGowan</namePart>
<affiliation>North Scotland Regional Genetics Service, Ashgrove House, Aberdeen, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Florence</namePart>
<namePart type="family">Petit</namePart>
<affiliation>Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU Lille, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Bruno</namePart>
<namePart type="family">Delobel</namePart>
<affiliation>Laboratoire de génétique chromosomique, Hôpital St Vincent de Paul, Lille, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Michael R</namePart>
<namePart type="family">Speicher</namePart>
<affiliation>Institute of Human Genetics, Medical University of Graz, Graz, Austria</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Paul</namePart>
<namePart type="family">Aurora</namePart>
<affiliation>Respiratory Medicine, Great Ormond Street Hospital, London, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">David</namePart>
<namePart type="family">Kilner</namePart>
<affiliation>Respiratory Medicine, Great Ormond Street Hospital, London, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Philippe</namePart>
<namePart type="family">Pellerin</namePart>
<affiliation>Centre de Référence des Malformations Cranio-maxillo-faciales Rares, CHRU Lille, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Marie</namePart>
<namePart type="family">Simon</namePart>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Jean-Paul</namePart>
<namePart type="family">Bonnefont</namePart>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Edward S</namePart>
<namePart type="family">Tobias</namePart>
<affiliation>School of Medicine, University of Glasgow, Yorkhill Hospital, Glasgow, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Sixto</namePart>
<namePart type="family">García-Miñaúr</namePart>
<affiliation>Institute for Medical and Molecular Genetics, La Paz University Hospital, Madrid, Spain</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Maria</namePart>
<namePart type="family">Bitner-Glindzicz</namePart>
<affiliation>Clinical and Molecular Genetics, Institute of Child Health, UCL, London, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Pernille</namePart>
<namePart type="family">Lindholm</namePart>
<affiliation>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Brigitte A</namePart>
<namePart type="family">Meijer</namePart>
<affiliation>Department of Oral and Maxillofacial Surgery, Kennemer Gasthuis, Haarlem, The Netherlands</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Véronique</namePart>
<namePart type="family">Abadie</namePart>
<affiliation>Service de Pédiatrie Générale, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Françoise</namePart>
<namePart type="family">Denoyelle</namePart>
<affiliation>INSERM UMR-S587 and Pediatric Otolaryngology Department, Armand-Trousseau Children's Hospital, AP-HP, Paris 6 University, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Marie-Paule</namePart>
<namePart type="family">Vazquez</namePart>
<affiliation>Service de Chirurgie Maxillo-Faciale et Plastique, CRMR des Malformations de la Face et de la Cavité Buccale, Hôpital Necker-Enfants Malades, AP-HP, Paris, France</affiliation>
<affiliation>Université Paris 5, UFR de Médecine Paris-Descartes, Paris, France</affiliation>
<affiliation>Centre de Recherche des Cordeliers, UMR S 872, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Christa</namePart>
<namePart type="family">Rotky-Fast</namePart>
<affiliation>Department of Pediatrics and Adolescence Medicine, Medical University of Graz, Graz, Austria</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Vincent</namePart>
<namePart type="family">Couloigner</namePart>
<affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Sébastien</namePart>
<namePart type="family">Pierrot</namePart>
<affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Yves</namePart>
<namePart type="family">Manach</namePart>
<affiliation>Service d'ORL Pediatrique, Hôpital Necker-Enfants Malades, AP-HP, Université Paris 5, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Sylvain</namePart>
<namePart type="family">Breton</namePart>
<affiliation>AP-HP, Service d'Imagerie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
<affiliation>Laboratoire d'Anatomie, Université Paris-Descartes, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Yvonne M C</namePart>
<namePart type="family">Hendriks</namePart>
<affiliation>Department of Clinical Genetics, Free University Medical Center, Amsterdam, The Netherlands</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Arnold</namePart>
<namePart type="family">Munnich</namePart>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Linda</namePart>
<namePart type="family">Jakobsen</namePart>
<affiliation>Department of Plastic and Reconstructive Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Peter</namePart>
<namePart type="family">Kroisel</namePart>
<affiliation>Institute of Human Genetics, Medical University of Graz, Graz, Austria</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Angela</namePart>
<namePart type="family">Lin</namePart>
<affiliation>Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts, USA</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Leonard B</namePart>
<namePart type="family">Kaban</namePart>
<affiliation>Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Lina</namePart>
<namePart type="family">Basel-Vanagaite</namePart>
<affiliation>Pediatric Genetics, Schneider Children's Medical Center of Israel and Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel</affiliation>
<affiliation>Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;</affiliation>
<affiliation>Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Louise</namePart>
<namePart type="family">Wilson</namePart>
<affiliation>North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Michael L</namePart>
<namePart type="family">Cunningham</namePart>
<affiliation>Center for Tissue and Cell Sciences, Seattle Children's Research Institute, Seattle, USA</affiliation>
<affiliation>Department of Pediatrics, University of Washington and Seattle Children's Hospital Craniofacial Center, Seattle, Washington, USA</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Stanislas</namePart>
<namePart type="family">Lyonnet</namePart>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Jeanne</namePart>
<namePart type="family">Amiel</namePart>
<affiliation>INSERM U781, Hôpital Necker-Enfants Malades and Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, Paris, France</affiliation>
<affiliation>AP-HP, Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<typeOfResource>text</typeOfResource>
<genre type="research-article" displayLabel="research-article"></genre>
<originInfo><publisher>BMJ Publishing Group Ltd</publisher>
<dateIssued encoding="w3cdtf">2013-03</dateIssued>
<dateCreated encoding="w3cdtf">2013-01-12</dateCreated>
<copyrightDate encoding="w3cdtf">2013</copyrightDate>
</originInfo>
<language><languageTerm type="code" authority="iso639-2b">eng</languageTerm>
<languageTerm type="code" authority="rfc3066">en</languageTerm>
</language>
<physicalDescription><internetMediaType>text/html</internetMediaType>
</physicalDescription>
<abstract>Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, β 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.</abstract>
<note type="footnotes"> CTG and AV contributed equally</note>
<subject><genre>keywords</genre>
<topic>PLCB4</topic>
<topic>GNAI3</topic>
<topic>auriculocondylar syndrome</topic>
<topic>question mark ear</topic>
<topic>micrognathia</topic>
</subject>
<relatedItem type="host"><titleInfo><title>Journal of Medical Genetics</title>
</titleInfo>
<titleInfo type="abbreviated"><title>J Med Genet</title>
</titleInfo>
<genre type="journal">journal</genre>
<identifier type="ISSN">0022-2593</identifier>
<identifier type="eISSN">1468-6244</identifier>
<identifier type="PublisherID">jmg</identifier>
<identifier type="PublisherID-hwp">jmedgenet</identifier>
<identifier type="PublisherID-nlm-ta">J Med Genet</identifier>
<part><date>2013</date>
<detail type="volume"><caption>vol.</caption>
<number>50</number>
</detail>
<detail type="issue"><caption>no.</caption>
<number>3</number>
</detail>
<extent unit="pages"><start>174</start>
</extent>
</part>
</relatedItem>
<identifier type="istex">7348F3B9E6763856063CA42E9C7451B169BAE498</identifier>
<identifier type="DOI">10.1136/jmedgenet-2012-101331</identifier>
<identifier type="href">jmedgenet-50-174.pdf</identifier>
<identifier type="ArticleID">jmedgenet-2012-101331</identifier>
<identifier type="PMID">23315542</identifier>
<identifier type="local">jmedgenet;50/3/174</identifier>
<accessCondition type="use and reproduction" contentType="copyright">Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</accessCondition>
<recordInfo><recordContentSource>BMJ</recordContentSource>
</recordInfo>
</mods>
</metadata>
<annexes><json:item><extension>jpeg</extension>
<original>true</original>
<mimetype>image/jpeg</mimetype>
<uri>https://api.istex.fr/document/7348F3B9E6763856063CA42E9C7451B169BAE498/annexes/jpeg</uri>
</json:item>
</annexes>
<serie></serie>
</istex>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002425 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 002425 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= ParkinsonFranceV1 |flux= Istex |étape= Corpus |type= RBID |clé= ISTEX:7348F3B9E6763856063CA42E9C7451B169BAE498 |texte= Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome }}
![]() | This area was generated with Dilib version V0.6.29. | ![]() |