Genomic deletions of OFD1 account for 23% of oral‐facial‐digital type 1 syndrome after negative DNA sequencing
Identifieur interne : 000C91 ( Istex/Corpus ); précédent : 000C90; suivant : 000C92Genomic deletions of OFD1 account for 23% of oral‐facial‐digital type 1 syndrome after negative DNA sequencing
Auteurs : Christel Thauvin-Robinet ; Brunella Franco ; Pascale Saugier-Veber ; Bernard Aral ; Nadège Gigot ; Anne Donzel ; Lionel Van Maldergem ; Eric Bieth ; Valérie Layet ; Michèle Mathieu ; Ahmad Teebi ; James Lespinasse ; Patrick Callier ; Francine Mugneret ; Alice Masurel-Paulet ; Elodie Gautier ; Frédéric Huet ; Jean-Raymond Teyssier ; Mario Tosi ; Thierry Frébourg ; Laurence FaivreSource :
- Human Mutation [ 1059-7794 ] ; 2009-02.
English descriptors
Abstract
Oral‐facial‐digital type I syndrome (OFDI) is characterised by an X‐linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and central nervous system malformations. Considerable allelic heterogeneity has been reported within the OFD1 gene, but DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene remains negative in more than 20% of cases. We hypothesized that genomic rearrangements could account for the majority of the remaining undiagnosed cases. Thus, we took advantage of two independent available series of patients with OFDI syndrome and negative DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene from two different European labs: 13/36 cases from the French lab; 13/95 from the Italian lab. All patients were screened by a semiquantitative fluorescent multiplex method (QFMPSF) and relative quantification by real‐time PCR (qPCR). Six OFD1 genomic deletions (exon 5, exons 1–8, exons 1–14, exons 10–11, exons 13–23 and exon 17) were identified, accounting for 5% of OFDI patients and for 23% of patients with negative mutation screening by DNA sequencing. The association of DNA direct sequencing, QFMPSF and qPCR detects OFD1 alteration in up to 85% of patients with a phenotype suggestive of OFDI syndrome. Given the average percentage of large genomic rearrangements (5%), we suggest that dosage methods should be performed in addition to DNA direct sequencing analysis to exclude the involvement of the OFD1 transcript when there are genetic counselling issues. © 2008 Wiley‐Liss, Inc.
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DOI: 10.1002/humu.20888
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sortKey="Lespinasse, James" sort="Lespinasse, James" uniqKey="Lespinasse J" first="James" last="Lespinasse">James Lespinasse</name><affiliation><mods:affiliation>Laboratoire de Génétique Chromosomique, CH Chambéry, France</mods:affiliation></affiliation></author><author><name sortKey="Callier, Patrick" sort="Callier, Patrick" uniqKey="Callier P" first="Patrick" last="Callier">Patrick Callier</name><affiliation><mods:affiliation>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Mugneret, Francine" sort="Mugneret, Francine" uniqKey="Mugneret F" first="Francine" last="Mugneret">Francine Mugneret</name><affiliation><mods:affiliation>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Masurel Aulet, Alice" sort="Masurel Aulet, Alice" uniqKey="Masurel Aulet A" first="Alice" last="Masurel-Paulet">Alice Masurel-Paulet</name><affiliation><mods:affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Gautier, Elodie" sort="Gautier, Elodie" uniqKey="Gautier E" first="Elodie" last="Gautier">Elodie Gautier</name><affiliation><mods:affiliation>CIC‐EC, CHU Le Bocage, Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Huet, Frederic" sort="Huet, Frederic" uniqKey="Huet F" first="Frédéric" last="Huet">Frédéric Huet</name><affiliation><mods:affiliation>Service de Pédiatrie 1, Hôpital d'Enfants, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Teyssier, Jean Aymond" sort="Teyssier, Jean Aymond" uniqKey="Teyssier J" first="Jean-Raymond" last="Teyssier">Jean-Raymond Teyssier</name><affiliation><mods:affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Tosi, Mario" sort="Tosi, Mario" uniqKey="Tosi M" first="Mario" last="Tosi">Mario Tosi</name><affiliation><mods:affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</mods:affiliation></affiliation></author><author><name sortKey="Frebourg, Thierry" sort="Frebourg, Thierry" uniqKey="Frebourg T" first="Thierry" last="Frébourg">Thierry Frébourg</name><affiliation><mods:affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</mods:affiliation></affiliation></author><author><name sortKey="Faivre, Laurence" sort="Faivre, Laurence" uniqKey="Faivre L" first="Laurence" last="Faivre">Laurence Faivre</name><affiliation><mods:affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1002/humu.20888</idno><idno type="url">https://api.istex.fr/document/52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000C91</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Genomic deletions of OFD1 account for 23% of oral‐facial‐digital type 1 syndrome after negative DNA sequencing</title><author><name sortKey="Thauvin Obinet, Christel" sort="Thauvin Obinet, Christel" uniqKey="Thauvin Obinet C" first="Christel" last="Thauvin-Robinet">Christel Thauvin-Robinet</name><affiliation><mods:affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Franco, Brunella" sort="Franco, Brunella" uniqKey="Franco B" first="Brunella" last="Franco">Brunella Franco</name><affiliation><mods:affiliation>Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Medical Genetic Services, Department of Pediatrics, Federico II University of Naples, Italy</mods:affiliation></affiliation></author><author><name sortKey="Saugier Eber, Pascale" sort="Saugier Eber, Pascale" uniqKey="Saugier Eber P" first="Pascale" last="Saugier-Veber">Pascale Saugier-Veber</name><affiliation><mods:affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</mods:affiliation></affiliation></author><author><name sortKey="Aral, Bernard" sort="Aral, Bernard" uniqKey="Aral B" first="Bernard" last="Aral">Bernard Aral</name><affiliation><mods:affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Gigot, Nadege" sort="Gigot, Nadege" uniqKey="Gigot N" first="Nadège" last="Gigot">Nadège Gigot</name><affiliation><mods:affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Donzel, Anne" sort="Donzel, Anne" uniqKey="Donzel A" first="Anne" last="Donzel">Anne Donzel</name><affiliation><mods:affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Van Maldergem, Lionel" sort="Van Maldergem, Lionel" uniqKey="Van Maldergem L" first="Lionel" last="Van Maldergem">Lionel Van Maldergem</name><affiliation><mods:affiliation>Institut de Pathologie et de Génétique, Loverval, Belgique</mods:affiliation></affiliation></author><author><name sortKey="Bieth, Eric" sort="Bieth, Eric" uniqKey="Bieth E" first="Eric" last="Bieth">Eric Bieth</name><affiliation><mods:affiliation>Laboratoire de Génétique, CHU Purpan, Toulouse, France</mods:affiliation></affiliation></author><author><name sortKey="Layet, Valerie" sort="Layet, Valerie" uniqKey="Layet V" first="Valérie" last="Layet">Valérie Layet</name><affiliation><mods:affiliation>Unité de Cytogénétique et Génétique médicale, CH Le Havre, France</mods:affiliation></affiliation></author><author><name sortKey="Mathieu, Michele" sort="Mathieu, Michele" uniqKey="Mathieu M" first="Michèle" last="Mathieu">Michèle Mathieu</name><affiliation><mods:affiliation>Centre de référence ‐ Anomalies du développement et syndromes malformatifs – de la région Nord, Département de pédiatrie ‐ Unité de génétique clinique, CHU Hôpital Nord, Amiens</mods:affiliation></affiliation></author><author><name sortKey="Teebi, Ahmad" sort="Teebi, Ahmad" uniqKey="Teebi A" first="Ahmad" last="Teebi">Ahmad Teebi</name><affiliation><mods:affiliation>Weill Cornell Medical College in Qatar, Qatar Foundation‐Education City, Doha, Qatar</mods:affiliation></affiliation></author><author><name sortKey="Lespinasse, James" sort="Lespinasse, James" uniqKey="Lespinasse J" first="James" last="Lespinasse">James Lespinasse</name><affiliation><mods:affiliation>Laboratoire de Génétique Chromosomique, CH Chambéry, France</mods:affiliation></affiliation></author><author><name sortKey="Callier, Patrick" sort="Callier, Patrick" uniqKey="Callier P" first="Patrick" last="Callier">Patrick Callier</name><affiliation><mods:affiliation>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Mugneret, Francine" sort="Mugneret, Francine" uniqKey="Mugneret F" first="Francine" last="Mugneret">Francine Mugneret</name><affiliation><mods:affiliation>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Masurel Aulet, Alice" sort="Masurel Aulet, Alice" uniqKey="Masurel Aulet A" first="Alice" last="Masurel-Paulet">Alice Masurel-Paulet</name><affiliation><mods:affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Gautier, Elodie" sort="Gautier, Elodie" uniqKey="Gautier E" first="Elodie" last="Gautier">Elodie Gautier</name><affiliation><mods:affiliation>CIC‐EC, CHU Le Bocage, Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Huet, Frederic" sort="Huet, Frederic" uniqKey="Huet F" first="Frédéric" last="Huet">Frédéric Huet</name><affiliation><mods:affiliation>Service de Pédiatrie 1, Hôpital d'Enfants, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Teyssier, Jean Aymond" sort="Teyssier, Jean Aymond" uniqKey="Teyssier J" first="Jean-Raymond" last="Teyssier">Jean-Raymond Teyssier</name><affiliation><mods:affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Tosi, Mario" sort="Tosi, Mario" uniqKey="Tosi M" first="Mario" last="Tosi">Mario Tosi</name><affiliation><mods:affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</mods:affiliation></affiliation></author><author><name sortKey="Frebourg, Thierry" sort="Frebourg, Thierry" uniqKey="Frebourg T" first="Thierry" last="Frébourg">Thierry Frébourg</name><affiliation><mods:affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</mods:affiliation></affiliation></author><author><name sortKey="Faivre, Laurence" sort="Faivre, Laurence" uniqKey="Faivre L" first="Laurence" last="Faivre">Laurence Faivre</name><affiliation><mods:affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Mutation</title><title level="j" type="abbrev">Hum. Mutat.</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-02">2009-02</date><biblScope unit="volume">30</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="E320">E320</biblScope><biblScope unit="page" to="E329">E329</biblScope></imprint><idno type="ISSN">1059-7794</idno></series><idno type="istex">52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF</idno><idno type="DOI">10.1002/humu.20888</idno><idno type="ArticleID">HUMU20888</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>OFD1</term><term>QMPSF</term><term>deletions</term><term>large rearrangements</term><term>oral‐facial‐digital syndrome</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Oral‐facial‐digital type I syndrome (OFDI) is characterised by an X‐linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and central nervous system malformations. Considerable allelic heterogeneity has been reported within the OFD1 gene, but DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene remains negative in more than 20% of cases. We hypothesized that genomic rearrangements could account for the majority of the remaining undiagnosed cases. Thus, we took advantage of two independent available series of patients with OFDI syndrome and negative DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene from two different European labs: 13/36 cases from the French lab; 13/95 from the Italian lab. All patients were screened by a semiquantitative fluorescent multiplex method (QFMPSF) and relative quantification by real‐time PCR (qPCR). Six OFD1 genomic deletions (exon 5, exons 1–8, exons 1–14, exons 10–11, exons 13–23 and exon 17) were identified, accounting for 5% of OFDI patients and for 23% of patients with negative mutation screening by DNA sequencing. The association of DNA direct sequencing, QFMPSF and qPCR detects OFD1 alteration in up to 85% of patients with a phenotype suggestive of OFDI syndrome. Given the average percentage of large genomic rearrangements (5%), we suggest that dosage methods should be performed in addition to DNA direct sequencing analysis to exclude the involvement of the OFD1 transcript when there are genetic counselling issues. © 2008 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Christel Thauvin‐Robinet</name><affiliations><json:string>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</json:string><json:string>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</json:string></affiliations></json:item><json:item><name>Brunella Franco</name><affiliations><json:string>Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy</json:string><json:string>Medical Genetic Services, Department of Pediatrics, Federico II University of Naples, Italy</json:string></affiliations></json:item><json:item><name>Pascale Saugier‐Veber</name><affiliations><json:string>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</json:string></affiliations></json:item><json:item><name>Bernard Aral</name><affiliations><json:string>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</json:string></affiliations></json:item><json:item><name>Nadège Gigot</name><affiliations><json:string>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</json:string></affiliations></json:item><json:item><name>Anne Donzel</name><affiliations><json:string>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</json:string></affiliations></json:item><json:item><name>Lionel Van Maldergem</name><affiliations><json:string>Institut de Pathologie et de Génétique, Loverval, Belgique</json:string></affiliations></json:item><json:item><name>Eric Bieth</name><affiliations><json:string>Laboratoire de Génétique, CHU Purpan, Toulouse, France</json:string></affiliations></json:item><json:item><name>Valérie Layet</name><affiliations><json:string>Unité de Cytogénétique et Génétique médicale, CH Le Havre, France</json:string></affiliations></json:item><json:item><name>Michèle Mathieu</name><affiliations><json:string>Centre de référence ‐ Anomalies du développement et syndromes malformatifs – de la région Nord, Département de pédiatrie ‐ Unité de génétique clinique, CHU Hôpital Nord, Amiens</json:string></affiliations></json:item><json:item><name>Ahmad Teebi</name><affiliations><json:string>Weill Cornell Medical College in Qatar, Qatar Foundation‐Education City, Doha, Qatar</json:string></affiliations></json:item><json:item><name>James Lespinasse</name><affiliations><json:string>Laboratoire de Génétique Chromosomique, CH Chambéry, France</json:string></affiliations></json:item><json:item><name>Patrick Callier</name><affiliations><json:string>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</json:string></affiliations></json:item><json:item><name>Francine Mugneret</name><affiliations><json:string>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</json:string></affiliations></json:item><json:item><name>Alice Masurel‐Paulet</name><affiliations><json:string>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</json:string><json:string>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</json:string></affiliations></json:item><json:item><name>Elodie Gautier</name><affiliations><json:string>CIC‐EC, CHU Le Bocage, Dijon, France</json:string></affiliations></json:item><json:item><name>Frédéric Huet</name><affiliations><json:string>Service de Pédiatrie 1, Hôpital d'Enfants, CHU Dijon, France</json:string></affiliations></json:item><json:item><name>Jean‐Raymond Teyssier</name><affiliations><json:string>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</json:string></affiliations></json:item><json:item><name>Mario Tosi</name><affiliations><json:string>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</json:string></affiliations></json:item><json:item><name>Thierry Frébourg</name><affiliations><json:string>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</json:string></affiliations></json:item><json:item><name>Laurence Faivre</name><affiliations><json:string>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</json:string><json:string>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>oral‐facial‐digital syndrome</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>OFD1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>deletions</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>large rearrangements</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>QMPSF</value></json:item></subject><articleId><json:string>HUMU20888</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>shortCommunication</json:string></originalGenre><abstract>Oral‐facial‐digital type I syndrome (OFDI) is characterised by an X‐linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and central nervous system malformations. Considerable allelic heterogeneity has been reported within the OFD1 gene, but DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene remains negative in more than 20% of cases. We hypothesized that genomic rearrangements could account for the majority of the remaining undiagnosed cases. Thus, we took advantage of two independent available series of patients with OFDI syndrome and negative DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene from two different European labs: 13/36 cases from the French lab; 13/95 from the Italian lab. All patients were screened by a semiquantitative fluorescent multiplex method (QFMPSF) and relative quantification by real‐time PCR (qPCR). Six OFD1 genomic deletions (exon 5, exons 1–8, exons 1–14, exons 10–11, exons 13–23 and exon 17) were identified, accounting for 5% of OFDI patients and for 23% of patients with negative mutation screening by DNA sequencing. The association of DNA direct sequencing, QFMPSF and qPCR detects OFD1 alteration in up to 85% of patients with a phenotype suggestive of OFDI syndrome. Given the average percentage of large genomic rearrangements (5%), we suggest that dosage methods should be performed in addition to DNA direct sequencing analysis to exclude the involvement of the OFD1 transcript when there are genetic counselling issues. © 2008 Wiley‐Liss, Inc.</abstract><qualityIndicators><score>7.59</score><pdfVersion>1.4</pdfVersion><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1691</abstractCharCount><pdfWordCount>4090</pdfWordCount><pdfCharCount>24333</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>251</abstractWordCount></qualityIndicators><title>Genomic deletions of OFD1 account for 23% of oral‐facial‐digital type 1 syndrome after negative DNA sequencing</title><genre><json:string>brief-communication</json:string></genre><host><volume>30</volume><publisherId><json:string>HUMU</json:string></publisherId><pages><total>10</total><last>E329</last><first>E320</first></pages><issn><json:string>1059-7794</json:string></issn><issue>2</issue><subject><json:item><value>Mutation in Brief</value></json:item></subject><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1098-1004</json:string></eissn><title>Human Mutation</title><doi><json:string>10.1002/(ISSN)1098-1004</json:string></doi></host><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1002/humu.20888</json:string></doi><id>52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF</id><score>0.19971475</score><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Genomic deletions of OFD1 account for 23% of oral‐facial‐digital type 1 syndrome after negative DNA sequencing</title><respStmt><resp>Références bibliographiques récupérées via GROBID</resp><name resp="ISTEX-API">ISTEX-API (INIST-CNRS)</name></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>© 2008 Wiley‐Liss, Inc.</p></availability><date>2009</date></publicationStmt><notesStmt><note type="content">*Communicated by Iain McIntosh</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Genomic deletions of OFD1 account for 23% of oral‐facial‐digital type 1 syndrome after negative DNA sequencing</title><author xml:id="author-1"><persName><forename type="first">Christel</forename><surname>Thauvin‐Robinet</surname></persName><note type="correspondence"><p>Correspondence: Centre de Génétique, Hôpital d'Enfants, 10 Bd maréchal de Lattre de Tassigny, 21034 Dijon cédex, France, Tel: 33 3 80 29 53 13, Fax 33 3 80 29 32 66</p></note><affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</affiliation><affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</affiliation></author><author xml:id="author-2"><persName><forename type="first">Brunella</forename><surname>Franco</surname></persName><affiliation>Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy</affiliation><affiliation>Medical Genetic Services, Department of Pediatrics, Federico II University of Naples, Italy</affiliation></author><author xml:id="author-3"><persName><forename type="first">Pascale</forename><surname>Saugier‐Veber</surname></persName><affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</affiliation></author><author xml:id="author-4"><persName><forename type="first">Bernard</forename><surname>Aral</surname></persName><affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</affiliation></author><author xml:id="author-5"><persName><forename type="first">Nadège</forename><surname>Gigot</surname></persName><affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</affiliation></author><author xml:id="author-6"><persName><forename type="first">Anne</forename><surname>Donzel</surname></persName><affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</affiliation></author><author xml:id="author-7"><persName><forename type="first">Lionel</forename><surname>Van Maldergem</surname></persName><affiliation>Institut de Pathologie et de Génétique, Loverval, Belgique</affiliation></author><author xml:id="author-8"><persName><forename type="first">Eric</forename><surname>Bieth</surname></persName><affiliation>Laboratoire de Génétique, CHU Purpan, Toulouse, France</affiliation></author><author xml:id="author-9"><persName><forename type="first">Valérie</forename><surname>Layet</surname></persName><affiliation>Unité de Cytogénétique et Génétique médicale, CH Le Havre, France</affiliation></author><author xml:id="author-10"><persName><forename type="first">Michèle</forename><surname>Mathieu</surname></persName><affiliation>Centre de référence ‐ Anomalies du développement et syndromes malformatifs – de la région Nord, Département de pédiatrie ‐ Unité de génétique clinique, CHU Hôpital Nord, Amiens</affiliation></author><author xml:id="author-11"><persName><forename type="first">Ahmad</forename><surname>Teebi</surname></persName><affiliation>Weill Cornell Medical College in Qatar, Qatar Foundation‐Education City, Doha, Qatar</affiliation></author><author xml:id="author-12"><persName><forename type="first">James</forename><surname>Lespinasse</surname></persName><affiliation>Laboratoire de Génétique Chromosomique, CH Chambéry, France</affiliation></author><author xml:id="author-13"><persName><forename type="first">Patrick</forename><surname>Callier</surname></persName><affiliation>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</affiliation></author><author xml:id="author-14"><persName><forename type="first">Francine</forename><surname>Mugneret</surname></persName><affiliation>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</affiliation></author><author xml:id="author-15"><persName><forename type="first">Alice</forename><surname>Masurel‐Paulet</surname></persName><affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</affiliation><affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</affiliation></author><author xml:id="author-16"><persName><forename type="first">Elodie</forename><surname>Gautier</surname></persName><affiliation>CIC‐EC, CHU Le Bocage, Dijon, France</affiliation></author><author xml:id="author-17"><persName><forename type="first">Frédéric</forename><surname>Huet</surname></persName><affiliation>Service de Pédiatrie 1, Hôpital d'Enfants, CHU Dijon, France</affiliation></author><author xml:id="author-18"><persName><forename type="first">Jean‐Raymond</forename><surname>Teyssier</surname></persName><affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</affiliation></author><author xml:id="author-19"><persName><forename type="first">Mario</forename><surname>Tosi</surname></persName><affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</affiliation></author><author xml:id="author-20"><persName><forename type="first">Thierry</forename><surname>Frébourg</surname></persName><affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</affiliation></author><author xml:id="author-21"><persName><forename type="first">Laurence</forename><surname>Faivre</surname></persName><affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</affiliation><affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</affiliation></author></analytic><monogr><title level="j">Human Mutation</title><title level="j" type="abbrev">Hum. Mutat.</title><idno type="pISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><idno type="DOI">10.1002/(ISSN)1098-1004</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-02"></date><biblScope unit="volume">30</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="E320">E320</biblScope><biblScope unit="page" to="E329">E329</biblScope></imprint></monogr><idno type="istex">52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF</idno><idno type="DOI">10.1002/humu.20888</idno><idno type="ArticleID">HUMU20888</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Oral‐facial‐digital type I syndrome (OFDI) is characterised by an X‐linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and central nervous system malformations. Considerable allelic heterogeneity has been reported within the OFD1 gene, but DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene remains negative in more than 20% of cases. We hypothesized that genomic rearrangements could account for the majority of the remaining undiagnosed cases. Thus, we took advantage of two independent available series of patients with OFDI syndrome and negative DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene from two different European labs: 13/36 cases from the French lab; 13/95 from the Italian lab. All patients were screened by a semiquantitative fluorescent multiplex method (QFMPSF) and relative quantification by real‐time PCR (qPCR). Six OFD1 genomic deletions (exon 5, exons 1–8, exons 1–14, exons 10–11, exons 13–23 and exon 17) were identified, accounting for 5% of OFDI patients and for 23% of patients with negative mutation screening by DNA sequencing. The association of DNA direct sequencing, QFMPSF and qPCR detects OFD1 alteration in up to 85% of patients with a phenotype suggestive of OFDI syndrome. Given the average percentage of large genomic rearrangements (5%), we suggest that dosage methods should be performed in addition to DNA direct sequencing analysis to exclude the involvement of the OFD1 transcript when there are genetic counselling issues. © 2008 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>oral‐facial‐digital syndrome</term></item><item><term>OFD1</term></item><item><term>deletions</term></item><item><term>large rearrangements</term></item><item><term>QMPSF</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Mutation in Brief</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-05-29">Received</change><change when="2008-07-25">Registration</change><change when="2009-02">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-10-24">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley component found"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1098-1004</doi><issn type="print">1059-7794</issn><issn type="electronic">1098-1004</issn><idGroup><id type="product" value="HUMU"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="HUMAN MUTATION">Human Mutation</title><title type="short">Hum. 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France</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="FR" type="organization"><unparsedAffiliation>Unité de Cytogénétique et Génétique médicale, CH Le Havre, France</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="US" type="organization"><unparsedAffiliation>Centre de référence ‐ Anomalies du développement et syndromes malformatifs – de la région Nord, Département de pédiatrie ‐ Unité de génétique clinique, CHU Hôpital Nord, Amiens</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="US" type="organization"><unparsedAffiliation>Weill Cornell Medical College in Qatar, Qatar Foundation‐Education City, Doha, Qatar</unparsedAffiliation></affiliation><affiliation xml:id="af12" countryCode="FR" type="organization"><unparsedAffiliation>Laboratoire de Génétique Chromosomique, CH Chambéry, France</unparsedAffiliation></affiliation><affiliation xml:id="af13" countryCode="FR" type="organization"><unparsedAffiliation>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</unparsedAffiliation></affiliation><affiliation xml:id="af14" countryCode="FR" type="organization"><unparsedAffiliation>CIC‐EC, CHU Le Bocage, Dijon, France</unparsedAffiliation></affiliation><affiliation xml:id="af15" countryCode="FR" type="organization"><unparsedAffiliation>Service de Pédiatrie 1, Hôpital d'Enfants, CHU Dijon, France</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">oral‐facial‐digital syndrome</keyword><keyword xml:id="kwd2">OFD1</keyword><keyword xml:id="kwd3">deletions</keyword><keyword xml:id="kwd4">large rearrangements</keyword><keyword xml:id="kwd5">QMPSF</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Oral‐facial‐digital type I syndrome (OFDI) is characterised by an X‐linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and central nervous system malformations. Considerable allelic heterogeneity has been reported within the <i>OFD1</i> gene, but DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the <i>OFD1</i> gene remains negative in more than 20% of cases. We hypothesized that genomic rearrangements could account for the majority of the remaining undiagnosed cases. Thus, we took advantage of two independent available series of patients with OFDI syndrome and negative DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the <i>OFD1</i> gene from two different European labs: 13/36 cases from the French lab; 13/95 from the Italian lab. All patients were screened by a semiquantitative fluorescent multiplex method (QFMPSF) and relative quantification by real‐time PCR (qPCR). Six <i>OFD1</i> genomic deletions (exon 5, exons 1–8, exons 1–14, exons 10–11, exons 13–23 and exon 17) were identified, accounting for 5% of OFDI patients and for 23% of patients with negative mutation screening by DNA sequencing. The association of DNA direct sequencing, QFMPSF and qPCR detects OFD1 alteration in up to 85% of patients with a phenotype suggestive of OFDI syndrome. Given the average percentage of large genomic rearrangements (5%), we suggest that dosage methods should be performed in addition to DNA direct sequencing analysis to exclude the involvement of the OFD1 transcript when there are genetic counselling issues. © 2008 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Communicated by Iain McIntosh</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Genomic deletions of OFD1 account for 23% of oral‐facial‐digital type 1 syndrome after negative DNA sequencing</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>OFD1 and Genomic Deletions</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Genomic deletions of OFD1 account for 23% of oral‐facial‐digital type 1 syndrome after negative DNA sequencing</title></titleInfo><name type="personal"><namePart type="given">Christel</namePart><namePart type="family">Thauvin‐Robinet</namePart><affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</affiliation><affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</affiliation><description>Correspondence: Centre de Génétique, Hôpital d'Enfants, 10 Bd maréchal de Lattre de Tassigny, 21034 Dijon cédex, France, Tel: 33 3 80 29 53 13, Fax 33 3 80 29 32 66</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Brunella</namePart><namePart type="family">Franco</namePart><affiliation>Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy</affiliation><affiliation>Medical Genetic Services, Department of Pediatrics, Federico II University of Naples, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Pascale</namePart><namePart type="family">Saugier‐Veber</namePart><affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bernard</namePart><namePart type="family">Aral</namePart><affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nadège</namePart><namePart type="family">Gigot</namePart><affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anne</namePart><namePart type="family">Donzel</namePart><affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lionel</namePart><namePart type="family">Van Maldergem</namePart><affiliation>Institut de Pathologie et de Génétique, Loverval, Belgique</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eric</namePart><namePart type="family">Bieth</namePart><affiliation>Laboratoire de Génétique, CHU Purpan, Toulouse, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Valérie</namePart><namePart type="family">Layet</namePart><affiliation>Unité de Cytogénétique et Génétique médicale, CH Le Havre, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michèle</namePart><namePart type="family">Mathieu</namePart><affiliation>Centre de référence ‐ Anomalies du développement et syndromes malformatifs – de la région Nord, Département de pédiatrie ‐ Unité de génétique clinique, CHU Hôpital Nord, Amiens</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ahmad</namePart><namePart type="family">Teebi</namePart><affiliation>Weill Cornell Medical College in Qatar, Qatar Foundation‐Education City, Doha, Qatar</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">James</namePart><namePart type="family">Lespinasse</namePart><affiliation>Laboratoire de Génétique Chromosomique, CH Chambéry, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrick</namePart><namePart type="family">Callier</namePart><affiliation>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Francine</namePart><namePart type="family">Mugneret</namePart><affiliation>Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alice</namePart><namePart type="family">Masurel‐Paulet</namePart><affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</affiliation><affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elodie</namePart><namePart type="family">Gautier</namePart><affiliation>CIC‐EC, CHU Le Bocage, Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Frédéric</namePart><namePart type="family">Huet</namePart><affiliation>Service de Pédiatrie 1, Hôpital d'Enfants, CHU Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean‐Raymond</namePart><namePart type="family">Teyssier</namePart><affiliation>Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mario</namePart><namePart type="family">Tosi</namePart><affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thierry</namePart><namePart type="family">Frébourg</namePart><affiliation>Laboratoire de génétique moléculaire, CHU Rouen, et Inserm U614, Institut Hospitalo‐Universitaire de Recherche BioMédicale, Université de Rouen, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Laurence</namePart><namePart type="family">Faivre</namePart><affiliation>Centre de Génétique, Hôpital d'Enfants, CHU Dijon, France</affiliation><affiliation>Centre de Référence Maladies Rares ‐ Anomalies du Développement et syndromes malformatifs‐ de l'Interrégion Est, CHU Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="brief-communication" displayLabel="shortCommunication"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2009-02</dateIssued><dateCaptured encoding="w3cdtf">2008-05-29</dateCaptured><dateValid encoding="w3cdtf">2008-07-25</dateValid><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Oral‐facial‐digital type I syndrome (OFDI) is characterised by an X‐linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and central nervous system malformations. Considerable allelic heterogeneity has been reported within the OFD1 gene, but DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene remains negative in more than 20% of cases. We hypothesized that genomic rearrangements could account for the majority of the remaining undiagnosed cases. Thus, we took advantage of two independent available series of patients with OFDI syndrome and negative DNA bi‐directional sequencing of the exons and intron‐exon boundaries of the OFD1 gene from two different European labs: 13/36 cases from the French lab; 13/95 from the Italian lab. All patients were screened by a semiquantitative fluorescent multiplex method (QFMPSF) and relative quantification by real‐time PCR (qPCR). Six OFD1 genomic deletions (exon 5, exons 1–8, exons 1–14, exons 10–11, exons 13–23 and exon 17) were identified, accounting for 5% of OFDI patients and for 23% of patients with negative mutation screening by DNA sequencing. The association of DNA direct sequencing, QFMPSF and qPCR detects OFD1 alteration in up to 85% of patients with a phenotype suggestive of OFDI syndrome. Given the average percentage of large genomic rearrangements (5%), we suggest that dosage methods should be performed in addition to DNA direct sequencing analysis to exclude the involvement of the OFD1 transcript when there are genetic counselling issues. © 2008 Wiley‐Liss, Inc.</abstract><note type="content">*Communicated by Iain McIntosh</note><subject lang="en"><genre>keywords</genre><topic>oral‐facial‐digital syndrome</topic><topic>OFD1</topic><topic>deletions</topic><topic>large rearrangements</topic><topic>QMPSF</topic></subject><relatedItem type="host"><titleInfo><title>Human Mutation</title></titleInfo><titleInfo type="abbreviated"><title>Hum. Mutat.</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Mutation in Brief</topic></subject><identifier type="ISSN">1059-7794</identifier><identifier type="eISSN">1098-1004</identifier><identifier type="DOI">10.1002/(ISSN)1098-1004</identifier><identifier type="PublisherID">HUMU</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>30</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>E320</start><end>E329</end><total>10</total></extent></part></relatedItem><identifier type="istex">52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF</identifier><identifier type="DOI">10.1002/humu.20888</identifier><identifier type="ArticleID">HUMU20888</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2008 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><enrichments><json:item><type>multicat</type><uri>https://api.istex.fr/document/52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF/enrichments/multicat</uri></json:item><json:item><type>refBibs</type><uri>https://api.istex.fr/document/52B0CD50483ADB60C97B1E9ACFA50FBE7B8D5AAF/enrichments/refBibs</uri></json:item></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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