LymphedemaV1, Pmc, Corpus, bibRecord, 001E53

Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy

Identifieur interne : 001E53 ( Pmc/Corpus ); précédent : 001E52; suivant : 001E54

Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy

Auteurs : Pia Ostergaard ; Michael A. Simpson ; Antonella Mendola ; Pradeep Vasudevan ; Fiona C. Connell ; Andreas Van Impel ; Anthony T. Moore ; Bart L. Loeys ; Arash Ghalamkarpour ; Alexandros Onoufriadis ; Ines Martinez-Corral ; Sophie Devery ; Jules G. Leroy ; Lut Van Laer ; Amihood Singer ; Martin G. Bialer ; Meriel Mcentagart ; Oliver Quarrell ; Glen Brice ; Richard C. Trembath ; Stefan Schulte-Merker ; Taija Makinen ; Miikka Vikkula ; Peter S. Mortimer ; Sahar Mansour ; Steve Jeffery

Source :

American Journal of Human Genetics [ 0002-9297 ] ; 2012.

RBID : PMC:3276660

Abstract

We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. KIF11 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of KIF11 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276660

DOI: 10.1016/j.ajhg.2011.12.018
PubMed: 22284827
PubMed Central: 3276660

Links to Exploration step

PMC:3276660

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mutations in <italic>KIF11</italic>
 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy</title>
<author><name sortKey="Ostergaard, Pia" sort="Ostergaard, Pia" uniqKey="Ostergaard P" first="Pia" last="Ostergaard">Pia Ostergaard</name>
<affiliation><nlm:aff id="aff1">Medical Genetics Unit, Biomedical Sciences, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Simpson, Michael A" sort="Simpson, Michael A" uniqKey="Simpson M" first="Michael A." last="Simpson">Michael A. Simpson</name>
<affiliation><nlm:aff id="aff2">Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mendola, Antonella" sort="Mendola, Antonella" uniqKey="Mendola A" first="Antonella" last="Mendola">Antonella Mendola</name>
<affiliation><nlm:aff id="aff3">Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vasudevan, Pradeep" sort="Vasudevan, Pradeep" uniqKey="Vasudevan P" first="Pradeep" last="Vasudevan">Pradeep Vasudevan</name>
<affiliation><nlm:aff id="aff4">Clinical Genetics, University Hospitals of Leicester National Health Services Trust, Leicester Royal Infirmary, Leicester LE1 5WW, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Connell, Fiona C" sort="Connell, Fiona C" uniqKey="Connell F" first="Fiona C." last="Connell">Fiona C. Connell</name>
<affiliation><nlm:aff id="aff5">Clinical Genetics, Guy's and St. Thomas' National Health Services Foundation Trust, Guy's Hospital, London SE1 9RT, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Impel, Andreas" sort="Van Impel, Andreas" uniqKey="Van Impel A" first="Andreas" last="Van Impel">Andreas Van Impel</name>
<affiliation><nlm:aff id="aff6">Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht, 3584 CT Utrecht, Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moore, Anthony T" sort="Moore, Anthony T" uniqKey="Moore A" first="Anthony T." last="Moore">Anthony T. Moore</name>
<affiliation><nlm:aff id="aff7">University College London Institute of Ophthalmology, Moorfields Eye Hospital and Hospital for Children, London EC1V 2PD, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Loeys, Bart L" sort="Loeys, Bart L" uniqKey="Loeys B" first="Bart L." last="Loeys">Bart L. Loeys</name>
<affiliation><nlm:aff id="aff8">Center for Medical Genetics, Antwerp University Hospital and University of Antwerp, B-2650 Antwerp, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ghalamkarpour, Arash" sort="Ghalamkarpour, Arash" uniqKey="Ghalamkarpour A" first="Arash" last="Ghalamkarpour">Arash Ghalamkarpour</name>
<affiliation><nlm:aff id="aff3">Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Onoufriadis, Alexandros" sort="Onoufriadis, Alexandros" uniqKey="Onoufriadis A" first="Alexandros" last="Onoufriadis">Alexandros Onoufriadis</name>
<affiliation><nlm:aff id="aff2">Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Martinez Corral, Ines" sort="Martinez Corral, Ines" uniqKey="Martinez Corral I" first="Ines" last="Martinez-Corral">Ines Martinez-Corral</name>
<affiliation><nlm:aff id="aff9">Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, U</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Devery, Sophie" sort="Devery, Sophie" uniqKey="Devery S" first="Sophie" last="Devery">Sophie Devery</name>
<affiliation><nlm:aff id="aff10">Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Leroy, Jules G" sort="Leroy, Jules G" uniqKey="Leroy J" first="Jules G." last="Leroy">Jules G. Leroy</name>
<affiliation><nlm:aff id="aff11">C. Hooft Children's Hospital, Ghent University Hospital, B-9000 Ghent, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Laer, Lut" sort="Van Laer, Lut" uniqKey="Van Laer L" first="Lut" last="Van Laer">Lut Van Laer</name>
<affiliation><nlm:aff id="aff8">Center for Medical Genetics, Antwerp University Hospital and University of Antwerp, B-2650 Antwerp, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Singer, Amihood" sort="Singer, Amihood" uniqKey="Singer A" first="Amihood" last="Singer">Amihood Singer</name>
<affiliation><nlm:aff id="aff12">Pediatrics and Medical Genetics, Barzilai Medical Center, 78306 Ashkelon, Israel</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bialer, Martin G" sort="Bialer, Martin G" uniqKey="Bialer M" first="Martin G." last="Bialer">Martin G. Bialer</name>
<affiliation><nlm:aff id="aff13">Division of Medical Genetics, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcentagart, Meriel" sort="Mcentagart, Meriel" uniqKey="Mcentagart M" first="Meriel" last="Mcentagart">Meriel Mcentagart</name>
<affiliation><nlm:aff id="aff14">South West Thames Regional Genetics Service, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Quarrell, Oliver" sort="Quarrell, Oliver" uniqKey="Quarrell O" first="Oliver" last="Quarrell">Oliver Quarrell</name>
<affiliation><nlm:aff id="aff15">Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield S10 2TH, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brice, Glen" sort="Brice, Glen" uniqKey="Brice G" first="Glen" last="Brice">Glen Brice</name>
<affiliation><nlm:aff id="aff14">South West Thames Regional Genetics Service, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Trembath, Richard C" sort="Trembath, Richard C" uniqKey="Trembath R" first="Richard C." last="Trembath">Richard C. Trembath</name>
<affiliation><nlm:aff id="aff2">Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schulte Merker, Stefan" sort="Schulte Merker, Stefan" uniqKey="Schulte Merker S" first="Stefan" last="Schulte-Merker">Stefan Schulte-Merker</name>
<affiliation><nlm:aff id="aff6">Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht, 3584 CT Utrecht, Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Makinen, Taija" sort="Makinen, Taija" uniqKey="Makinen T" first="Taija" last="Makinen">Taija Makinen</name>
<affiliation><nlm:aff id="aff9">Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, U</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vikkula, Miikka" sort="Vikkula, Miikka" uniqKey="Vikkula M" first="Miikka" last="Vikkula">Miikka Vikkula</name>
<affiliation><nlm:aff id="aff3">Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16">Walloon Excellence in Lifesciences and Biotechnology, Université catholique de Louvain, B-1200 Brussels, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mortimer, Peter S" sort="Mortimer, Peter S" uniqKey="Mortimer P" first="Peter S." last="Mortimer">Peter S. Mortimer</name>
<affiliation><nlm:aff id="aff17">Department of Cardiac and Vascular Sciences, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mansour, Sahar" sort="Mansour, Sahar" uniqKey="Mansour S" first="Sahar" last="Mansour">Sahar Mansour</name>
<affiliation><nlm:aff id="aff14">South West Thames Regional Genetics Service, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jeffery, Steve" sort="Jeffery, Steve" uniqKey="Jeffery S" first="Steve" last="Jeffery">Steve Jeffery</name>
<affiliation><nlm:aff id="aff1">Medical Genetics Unit, Biomedical Sciences, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
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<idno type="doi">10.1016/j.ajhg.2011.12.018</idno>
<date when="2012">2012</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mutations in <italic>KIF11</italic>
 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy</title>
<author><name sortKey="Ostergaard, Pia" sort="Ostergaard, Pia" uniqKey="Ostergaard P" first="Pia" last="Ostergaard">Pia Ostergaard</name>
<affiliation><nlm:aff id="aff1">Medical Genetics Unit, Biomedical Sciences, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Simpson, Michael A" sort="Simpson, Michael A" uniqKey="Simpson M" first="Michael A." last="Simpson">Michael A. Simpson</name>
<affiliation><nlm:aff id="aff2">Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mendola, Antonella" sort="Mendola, Antonella" uniqKey="Mendola A" first="Antonella" last="Mendola">Antonella Mendola</name>
<affiliation><nlm:aff id="aff3">Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vasudevan, Pradeep" sort="Vasudevan, Pradeep" uniqKey="Vasudevan P" first="Pradeep" last="Vasudevan">Pradeep Vasudevan</name>
<affiliation><nlm:aff id="aff4">Clinical Genetics, University Hospitals of Leicester National Health Services Trust, Leicester Royal Infirmary, Leicester LE1 5WW, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Connell, Fiona C" sort="Connell, Fiona C" uniqKey="Connell F" first="Fiona C." last="Connell">Fiona C. Connell</name>
<affiliation><nlm:aff id="aff5">Clinical Genetics, Guy's and St. Thomas' National Health Services Foundation Trust, Guy's Hospital, London SE1 9RT, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Impel, Andreas" sort="Van Impel, Andreas" uniqKey="Van Impel A" first="Andreas" last="Van Impel">Andreas Van Impel</name>
<affiliation><nlm:aff id="aff6">Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht, 3584 CT Utrecht, Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moore, Anthony T" sort="Moore, Anthony T" uniqKey="Moore A" first="Anthony T." last="Moore">Anthony T. Moore</name>
<affiliation><nlm:aff id="aff7">University College London Institute of Ophthalmology, Moorfields Eye Hospital and Hospital for Children, London EC1V 2PD, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Loeys, Bart L" sort="Loeys, Bart L" uniqKey="Loeys B" first="Bart L." last="Loeys">Bart L. Loeys</name>
<affiliation><nlm:aff id="aff8">Center for Medical Genetics, Antwerp University Hospital and University of Antwerp, B-2650 Antwerp, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ghalamkarpour, Arash" sort="Ghalamkarpour, Arash" uniqKey="Ghalamkarpour A" first="Arash" last="Ghalamkarpour">Arash Ghalamkarpour</name>
<affiliation><nlm:aff id="aff3">Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Onoufriadis, Alexandros" sort="Onoufriadis, Alexandros" uniqKey="Onoufriadis A" first="Alexandros" last="Onoufriadis">Alexandros Onoufriadis</name>
<affiliation><nlm:aff id="aff2">Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Martinez Corral, Ines" sort="Martinez Corral, Ines" uniqKey="Martinez Corral I" first="Ines" last="Martinez-Corral">Ines Martinez-Corral</name>
<affiliation><nlm:aff id="aff9">Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, U</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Devery, Sophie" sort="Devery, Sophie" uniqKey="Devery S" first="Sophie" last="Devery">Sophie Devery</name>
<affiliation><nlm:aff id="aff10">Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Leroy, Jules G" sort="Leroy, Jules G" uniqKey="Leroy J" first="Jules G." last="Leroy">Jules G. Leroy</name>
<affiliation><nlm:aff id="aff11">C. Hooft Children's Hospital, Ghent University Hospital, B-9000 Ghent, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Laer, Lut" sort="Van Laer, Lut" uniqKey="Van Laer L" first="Lut" last="Van Laer">Lut Van Laer</name>
<affiliation><nlm:aff id="aff8">Center for Medical Genetics, Antwerp University Hospital and University of Antwerp, B-2650 Antwerp, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Singer, Amihood" sort="Singer, Amihood" uniqKey="Singer A" first="Amihood" last="Singer">Amihood Singer</name>
<affiliation><nlm:aff id="aff12">Pediatrics and Medical Genetics, Barzilai Medical Center, 78306 Ashkelon, Israel</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bialer, Martin G" sort="Bialer, Martin G" uniqKey="Bialer M" first="Martin G." last="Bialer">Martin G. Bialer</name>
<affiliation><nlm:aff id="aff13">Division of Medical Genetics, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcentagart, Meriel" sort="Mcentagart, Meriel" uniqKey="Mcentagart M" first="Meriel" last="Mcentagart">Meriel Mcentagart</name>
<affiliation><nlm:aff id="aff14">South West Thames Regional Genetics Service, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Quarrell, Oliver" sort="Quarrell, Oliver" uniqKey="Quarrell O" first="Oliver" last="Quarrell">Oliver Quarrell</name>
<affiliation><nlm:aff id="aff15">Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield S10 2TH, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brice, Glen" sort="Brice, Glen" uniqKey="Brice G" first="Glen" last="Brice">Glen Brice</name>
<affiliation><nlm:aff id="aff14">South West Thames Regional Genetics Service, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Trembath, Richard C" sort="Trembath, Richard C" uniqKey="Trembath R" first="Richard C." last="Trembath">Richard C. Trembath</name>
<affiliation><nlm:aff id="aff2">Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schulte Merker, Stefan" sort="Schulte Merker, Stefan" uniqKey="Schulte Merker S" first="Stefan" last="Schulte-Merker">Stefan Schulte-Merker</name>
<affiliation><nlm:aff id="aff6">Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht, 3584 CT Utrecht, Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Makinen, Taija" sort="Makinen, Taija" uniqKey="Makinen T" first="Taija" last="Makinen">Taija Makinen</name>
<affiliation><nlm:aff id="aff9">Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, U</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vikkula, Miikka" sort="Vikkula, Miikka" uniqKey="Vikkula M" first="Miikka" last="Vikkula">Miikka Vikkula</name>
<affiliation><nlm:aff id="aff3">Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16">Walloon Excellence in Lifesciences and Biotechnology, Université catholique de Louvain, B-1200 Brussels, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mortimer, Peter S" sort="Mortimer, Peter S" uniqKey="Mortimer P" first="Peter S." last="Mortimer">Peter S. Mortimer</name>
<affiliation><nlm:aff id="aff17">Department of Cardiac and Vascular Sciences, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mansour, Sahar" sort="Mansour, Sahar" uniqKey="Mansour S" first="Sahar" last="Mansour">Sahar Mansour</name>
<affiliation><nlm:aff id="aff14">South West Thames Regional Genetics Service, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jeffery, Steve" sort="Jeffery, Steve" uniqKey="Jeffery S" first="Steve" last="Jeffery">Steve Jeffery</name>
<affiliation><nlm:aff id="aff1">Medical Genetics Unit, Biomedical Sciences, St. George's University of London, London SW17 0RE, UK</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">American Journal of Human Genetics</title>
<idno type="ISSN">0002-9297</idno>
<idno type="eISSN">1537-6605</idno>
<imprint><date when="2012">2012</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p>We have identified <italic>KIF11</italic>
 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous <italic>KIF11</italic>
 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of <italic>KIF11</italic>
 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. <italic>KIF11</italic>
 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of <italic>KIF11</italic>
 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.</p>
</div>
</front>
</TEI>
<pmc article-type="brief-report"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Hum Genet</journal-id>
<journal-id journal-id-type="iso-abbrev">Am. J. Hum. Genet</journal-id>
<journal-title-group><journal-title>American Journal of Human Genetics</journal-title>
</journal-title-group>
<issn pub-type="ppub">0002-9297</issn>
<issn pub-type="epub">1537-6605</issn>
<publisher><publisher-name>Elsevier</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22284827</article-id>
<article-id pub-id-type="pmc">3276660</article-id>
<article-id pub-id-type="publisher-id">S0002-9297(11)00553-2</article-id>
<article-id pub-id-type="doi">10.1016/j.ajhg.2011.12.018</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Report</subject>
</subj-group>
</article-categories>
<title-group><article-title>Mutations in <italic>KIF11</italic>
 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Ostergaard</surname>
<given-names>Pia</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Simpson</surname>
<given-names>Michael A.</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mendola</surname>
<given-names>Antonella</given-names>
</name>
<xref rid="aff3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vasudevan</surname>
<given-names>Pradeep</given-names>
</name>
<xref rid="aff4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Connell</surname>
<given-names>Fiona C.</given-names>
</name>
<xref rid="aff5" ref-type="aff">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van Impel</surname>
<given-names>Andreas</given-names>
</name>
<xref rid="aff6" ref-type="aff">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moore</surname>
<given-names>Anthony T.</given-names>
</name>
<xref rid="aff7" ref-type="aff">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Loeys</surname>
<given-names>Bart L.</given-names>
</name>
<xref rid="aff8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ghalamkarpour</surname>
<given-names>Arash</given-names>
</name>
<xref rid="aff3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Onoufriadis</surname>
<given-names>Alexandros</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Martinez-Corral</surname>
<given-names>Ines</given-names>
</name>
<xref rid="aff9" ref-type="aff">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Devery</surname>
<given-names>Sophie</given-names>
</name>
<xref rid="aff10" ref-type="aff">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Leroy</surname>
<given-names>Jules G.</given-names>
</name>
<xref rid="aff11" ref-type="aff">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van Laer</surname>
<given-names>Lut</given-names>
</name>
<xref rid="aff8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Singer</surname>
<given-names>Amihood</given-names>
</name>
<xref rid="aff12" ref-type="aff">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bialer</surname>
<given-names>Martin G.</given-names>
</name>
<xref rid="aff13" ref-type="aff">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McEntagart</surname>
<given-names>Meriel</given-names>
</name>
<xref rid="aff14" ref-type="aff">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Quarrell</surname>
<given-names>Oliver</given-names>
</name>
<xref rid="aff15" ref-type="aff">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brice</surname>
<given-names>Glen</given-names>
</name>
<xref rid="aff14" ref-type="aff">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Trembath</surname>
<given-names>Richard C.</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schulte-Merker</surname>
<given-names>Stefan</given-names>
</name>
<xref rid="aff6" ref-type="aff">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Makinen</surname>
<given-names>Taija</given-names>
</name>
<xref rid="aff9" ref-type="aff">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vikkula</surname>
<given-names>Miikka</given-names>
</name>
<xref rid="aff3" ref-type="aff">3</xref>
<xref rid="aff16" ref-type="aff">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mortimer</surname>
<given-names>Peter S.</given-names>
</name>
<xref rid="aff17" ref-type="aff">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mansour</surname>
<given-names>Sahar</given-names>
</name>
<xref rid="aff14" ref-type="aff">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jeffery</surname>
<given-names>Steve</given-names>
</name>
<email>sggt100@sgul.ac.uk</email>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="cor1" ref-type="corresp">∗</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
Medical Genetics Unit, Biomedical Sciences, St. George's University of London, London SW17 0RE, UK</aff>
<aff id="aff2"><label>2</label>
Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK</aff>
<aff id="aff3"><label>3</label>
Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium</aff>
<aff id="aff4"><label>4</label>
Clinical Genetics, University Hospitals of Leicester National Health Services Trust, Leicester Royal Infirmary, Leicester LE1 5WW, UK</aff>
<aff id="aff5"><label>5</label>
Clinical Genetics, Guy's and St. Thomas' National Health Services Foundation Trust, Guy's Hospital, London SE1 9RT, UK</aff>
<aff id="aff6"><label>6</label>
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht, 3584 CT Utrecht, Netherlands</aff>
<aff id="aff7"><label>7</label>
University College London Institute of Ophthalmology, Moorfields Eye Hospital and Hospital for Children, London EC1V 2PD, UK</aff>
<aff id="aff8"><label>8</label>
Center for Medical Genetics, Antwerp University Hospital and University of Antwerp, B-2650 Antwerp, Belgium</aff>
<aff id="aff9"><label>9</label>
Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, U</aff>
<aff id="aff10"><label>10</label>
Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK</aff>
<aff id="aff11"><label>11</label>
C. Hooft Children's Hospital, Ghent University Hospital, B-9000 Ghent, Belgium</aff>
<aff id="aff12"><label>12</label>
Pediatrics and Medical Genetics, Barzilai Medical Center, 78306 Ashkelon, Israel</aff>
<aff id="aff13"><label>13</label>
Division of Medical Genetics, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA</aff>
<aff id="aff14"><label>14</label>
South West Thames Regional Genetics Service, St. George's University of London, London SW17 0RE, UK</aff>
<aff id="aff15"><label>15</label>
Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield S10 2TH, UK</aff>
<aff id="aff16"><label>16</label>
Walloon Excellence in Lifesciences and Biotechnology, Université catholique de Louvain, B-1200 Brussels, Belgium</aff>
<aff id="aff17"><label>17</label>
Department of Cardiac and Vascular Sciences, St. George's University of London, London SW17 0RE, UK</aff>
<author-notes><corresp id="cor1"><label>∗</label>
Corresponding author <email>sggt100@sgul.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><day>10</day>
<month>2</month>
<year>2012</year>
</pub-date>
<volume>90</volume>
<issue>2</issue>
<fpage>356</fpage>
<lpage>362</lpage>
<history><date date-type="received"><day>30</day>
<month>9</month>
<year>2011</year>
</date>
<date date-type="rev-recd"><day>23</day>
<month>11</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>26</day>
<month>12</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>© 2012 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved.</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>The American Society of Human Genetics</copyright-holder>
</permissions>
<abstract><p>We have identified <italic>KIF11</italic>
 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous <italic>KIF11</italic>
 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of <italic>KIF11</italic>
 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. <italic>KIF11</italic>
 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of <italic>KIF11</italic>
 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy

Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy

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