Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy
Identifieur interne : 000105 ( PascalFrancis/Corpus ); précédent : 000104; suivant : 000106Mutations 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 JefferySource :
- American journal of human genetics [ 0002-9297 ] ; 2012.
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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 KIFI11 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.
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Format Inist (serveur)
| NO : | PASCAL 12-0150136 INIST |
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| ET : | Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy |
| AU : | OSTERGAARD (Pia); SIMPSON (Michael A.); MENDOLA (Antonella); VASUDEVAN (Pradeep); CONNELL (Fiona C.); IMPEL (Andreas Van); MOORE (Anthony T.); LOEYS (Bart L.); GHALAMKARPOUR (Arash); ONOUFRIADIS (Alexandros); MARTINEZ-CORRAL (Ines); DEVERY (Sophie); LEROY (Jules G.); LAER (Lut Van); SINGER (Amihood); BIALER (Martin G.); MCENTAGART (Meriel); QUARRELL (Oliver); BRICE (Glen); TREMBATH (Richard C.); SCHULTE-MERKER (Stefan); MAKINEN (Taija); VIKKULA (Miikka); MORTIMER (Peter S.); MANSOUR (Sahar); JEFFERY (Steve) |
| AF : | Medical Genetics Unit, Biomedical Sciences, St. George's University of London/London SW17 0RE/Royaume-Uni (1 aut., 26 aut.); Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital/London SE1 9RT/Royaume-Uni (2 aut., 10 aut., 20 aut.); Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain/1200 Brussels/Belgique (3 aut., 9 aut., 23 aut.); Clinical Genetics, University Hospitals of Leicester National Health Services Trust, Leicester Royal Infirmary/Leicester LE1 5WW/Royaume-Uni (4 aut.); Clinical Genetics, Guy's and St. Thomas' National Health Services Foundation Trust, Guy's Hospital/London SE1 9RT/Royaume-Uni (5 aut.); Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht/3584 CT Utrecht/Pays-Bas (6 aut., 21 aut.); University College London Institute of Ophthalmology, Moorfields Eye Hospital and Hospital for Children/London EC1V 2PD/Royaume-Uni (7 aut.); Center for Medical Genetics, Antwerp University Hospital and University of Antwerp/2650 Antwerp/Belgique (8 aut., 14 aut.); Lymphatic Development Laboratory, Cancer Research UK London Research Institute/London WC2A 3PX/Royaume-Uni (11 aut., 22 aut.); Moorfields Eye Hospital NHS Foundation Trust/London EC1V 2PD/Royaume-Uni (12 aut.); C. Hooft Children's Hospital, Ghent University Hospital/9000 Ghent/Belgique (13 aut.); Paediatrics and Medical Genetics, Barzilai Medical Center/78306 Ashkelon/Israël (15 aut.); Division of Medical Genetics, North Shore-Long Island Jewish Health System/Manhasset, NY 11030/Etats-Unis (16 aut.); South West Thames Regional Genetics Service, St. George's University of London/London SW17 ORE/Royaume-Uni (17 aut., 19 aut., 25 aut.); Sheffield Clinical Genetics Service, Sheffield Children's Hospital/Sheffield S10 2TH/Royaume-Uni (18 aut.); Walloon Excellence in Lifesciences and Biotechnology, Université catholique de Louvain/1200 Brussels/Belgique (23 aut.); Department of Cardiac and Vascular Sciences, St. George's University of London/London SW17 0RE/Royaume-Uni (24 aut.) |
| DT : | Publication en série; Compte-rendu; Niveau analytique |
| SO : | American journal of human genetics; ISSN 0002-9297; Coden AJHGAG; Etats-Unis; Da. 2012; Vol. 90; No. 2; Pp. 356-362; Bibl. 24 ref. |
| LA : | Anglais |
| EA : | 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 KIFI11 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. |
| CC : | 002A04; 002A07; 002B23A; 002B17D |
| FD : | Microcéphalie; Lymphoedème; Choriorétinopathie; Mutation; Maladie héréditaire; Caractère autosomique; Caractère dominant; Congénital; Génétique; Homme |
| FG : | Pathologie de l'encéphale; Maladie congénitale; Malformation; Pathologie du système nerveux central; Pathologie du système nerveux; Pathologie de l'appareil circulatoire; Pathologie des vaisseaux lymphatiques; Pathologie de l'oeil; Rétinopathie; Pathologie de l'uvée |
| ED : | Microcephaly; Lymphedema; Chorioretinopathy; Mutation; Genetic disease; Autosomal character; Dominant character; Congenital; Genetics; Human |
| EG : | Cerebral disorder; Congenital disease; Malformation; Central nervous system disease; Nervous system diseases; Cardiovascular disease; Lymphatic vessel disease; Eye disease; Retinopathy; Uvea disease |
| SD : | Microcefalia; Linfedema; Coriorretinopatía; Mutación; Enfermedad hereditaria; Carácter autosómico; Carácter dominante; Congénito; Genética; Hombre |
| LO : | INIST-2610.354000509256020180 |
| ID : | 12-0150136 |
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Pascal:12-0150136Le document en format XML
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Moore</name><affiliation><inist:fA14 i1="07"><s1>University College London Institute of Ophthalmology, Moorfields Eye Hospital and Hospital for Children</s1><s2>London EC1V 2PD</s2><s3>GBR</s3><sZ>7 aut.</sZ></inist:fA14></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><inist:fA14 i1="08"><s1>Center for Medical Genetics, Antwerp University Hospital and University of Antwerp</s1><s2>2650 Antwerp</s2><s3>BEL</s3><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ghalamkarpour, Arash" sort="Ghalamkarpour, Arash" uniqKey="Ghalamkarpour A" first="Arash" last="Ghalamkarpour">Arash Ghalamkarpour</name><affiliation><inist:fA14 i1="03"><s1>Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain</s1><s2>1200 Brussels</s2><s3>BEL</s3><sZ>3 aut.</sZ><sZ>9 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Onoufriadis, Alexandros" sort="Onoufriadis, Alexandros" uniqKey="Onoufriadis A" first="Alexandros" last="Onoufriadis">Alexandros Onoufriadis</name><affiliation><inist:fA14 i1="02"><s1>Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital</s1><s2>London SE1 9RT</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ></inist:fA14></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><inist:fA14 i1="09"><s1>Lymphatic Development Laboratory, Cancer Research UK London Research Institute</s1><s2>London WC2A 3PX</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Devery, Sophie" sort="Devery, Sophie" uniqKey="Devery S" first="Sophie" last="Devery">Sophie Devery</name><affiliation><inist:fA14 i1="10"><s1>Moorfields Eye Hospital NHS Foundation Trust</s1><s2>London EC1V 2PD</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14></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><inist:fA14 i1="11"><s1>C. Hooft Children's Hospital, Ghent University Hospital</s1><s2>9000 Ghent</s2><s3>BEL</s3><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Laer, Lut Van" sort="Laer, Lut Van" uniqKey="Laer L" first="Lut Van" last="Laer">Lut Van Laer</name><affiliation><inist:fA14 i1="08"><s1>Center for Medical Genetics, Antwerp University Hospital and University of Antwerp</s1><s2>2650 Antwerp</s2><s3>BEL</s3><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Singer, Amihood" sort="Singer, Amihood" uniqKey="Singer A" first="Amihood" last="Singer">Amihood Singer</name><affiliation><inist:fA14 i1="12"><s1>Paediatrics and Medical Genetics, Barzilai Medical Center</s1><s2>78306 Ashkelon</s2><s3>ISR</s3><sZ>15 aut.</sZ></inist:fA14></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><inist:fA14 i1="13"><s1>Division of Medical Genetics, North Shore-Long Island Jewish Health System</s1><s2>Manhasset, NY 11030</s2><s3>USA</s3><sZ>16 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mcentagart, Meriel" sort="Mcentagart, Meriel" uniqKey="Mcentagart M" first="Meriel" last="Mcentagart">Meriel Mcentagart</name><affiliation><inist:fA14 i1="14"><s1>South West Thames Regional Genetics Service, St. George's University of London</s1><s2>London SW17 ORE</s2><s3>GBR</s3><sZ>17 aut.</sZ><sZ>19 aut.</sZ><sZ>25 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Quarrell, Oliver" sort="Quarrell, Oliver" uniqKey="Quarrell O" first="Oliver" last="Quarrell">Oliver Quarrell</name><affiliation><inist:fA14 i1="15"><s1>Sheffield Clinical Genetics Service, Sheffield Children's Hospital</s1><s2>Sheffield S10 2TH</s2><s3>GBR</s3><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Brice, Glen" sort="Brice, Glen" uniqKey="Brice G" first="Glen" last="Brice">Glen Brice</name><affiliation><inist:fA14 i1="14"><s1>South West Thames Regional Genetics Service, St. George's University of London</s1><s2>London SW17 ORE</s2><s3>GBR</s3><sZ>17 aut.</sZ><sZ>19 aut.</sZ><sZ>25 aut.</sZ></inist:fA14></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><inist:fA14 i1="02"><s1>Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital</s1><s2>London SE1 9RT</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ></inist:fA14></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><inist:fA14 i1="06"><s1>Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht</s1><s2>3584 CT Utrecht</s2><s3>NLD</s3><sZ>6 aut.</sZ><sZ>21 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Makinen, Taija" sort="Makinen, Taija" uniqKey="Makinen T" first="Taija" last="Makinen">Taija Makinen</name><affiliation><inist:fA14 i1="09"><s1>Lymphatic Development Laboratory, Cancer Research UK London Research Institute</s1><s2>London WC2A 3PX</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Vikkula, Miikka" sort="Vikkula, Miikka" uniqKey="Vikkula M" first="Miikka" last="Vikkula">Miikka Vikkula</name><affiliation><inist:fA14 i1="03"><s1>Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain</s1><s2>1200 Brussels</s2><s3>BEL</s3><sZ>3 aut.</sZ><sZ>9 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="16"><s1>Walloon Excellence in Lifesciences and Biotechnology, Université catholique de Louvain</s1><s2>1200 Brussels</s2><s3>BEL</s3><sZ>23 aut.</sZ></inist:fA14></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><inist:fA14 i1="17"><s1>Department of Cardiac and Vascular Sciences, St. George's University of London</s1><s2>London SW17 0RE</s2><s3>GBR</s3><sZ>24 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mansour, Sahar" sort="Mansour, Sahar" uniqKey="Mansour S" first="Sahar" last="Mansour">Sahar Mansour</name><affiliation><inist:fA14 i1="14"><s1>South West Thames Regional Genetics Service, St. George's University of London</s1><s2>London SW17 ORE</s2><s3>GBR</s3><sZ>17 aut.</sZ><sZ>19 aut.</sZ><sZ>25 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Jeffery, Steve" sort="Jeffery, Steve" uniqKey="Jeffery S" first="Steve" last="Jeffery">Steve Jeffery</name><affiliation><inist:fA14 i1="01"><s1>Medical Genetics Unit, Biomedical Sciences, St. George's University of London</s1><s2>London SW17 0RE</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>26 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0150136</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0150136 INIST</idno><idno type="RBID">Pascal:12-0150136</idno><idno type="wicri:Area/PascalFrancis/Corpus">000105</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Mutations in KIF11 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><inist:fA14 i1="01"><s1>Medical Genetics Unit, Biomedical Sciences, St. George's University of London</s1><s2>London SW17 0RE</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>26 aut.</sZ></inist:fA14></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><inist:fA14 i1="02"><s1>Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital</s1><s2>London SE1 9RT</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mendola, Antonella" sort="Mendola, Antonella" uniqKey="Mendola A" first="Antonella" last="Mendola">Antonella Mendola</name><affiliation><inist:fA14 i1="03"><s1>Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain</s1><s2>1200 Brussels</s2><s3>BEL</s3><sZ>3 aut.</sZ><sZ>9 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Vasudevan, Pradeep" sort="Vasudevan, Pradeep" uniqKey="Vasudevan P" first="Pradeep" last="Vasudevan">Pradeep Vasudevan</name><affiliation><inist:fA14 i1="04"><s1>Clinical Genetics, University Hospitals of Leicester National Health Services Trust, Leicester Royal Infirmary</s1><s2>Leicester LE1 5WW</s2><s3>GBR</s3><sZ>4 aut.</sZ></inist:fA14></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><inist:fA14 i1="05"><s1>Clinical Genetics, Guy's and St. Thomas' National Health Services Foundation Trust, Guy's Hospital</s1><s2>London SE1 9RT</s2><s3>GBR</s3><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Impel, Andreas Van" sort="Impel, Andreas Van" uniqKey="Impel A" first="Andreas Van" last="Impel">Andreas Van Impel</name><affiliation><inist:fA14 i1="06"><s1>Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht</s1><s2>3584 CT Utrecht</s2><s3>NLD</s3><sZ>6 aut.</sZ><sZ>21 aut.</sZ></inist:fA14></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><inist:fA14 i1="07"><s1>University College London Institute of Ophthalmology, Moorfields Eye Hospital and Hospital for Children</s1><s2>London EC1V 2PD</s2><s3>GBR</s3><sZ>7 aut.</sZ></inist:fA14></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><inist:fA14 i1="08"><s1>Center for Medical Genetics, Antwerp University Hospital and University of Antwerp</s1><s2>2650 Antwerp</s2><s3>BEL</s3><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ghalamkarpour, Arash" sort="Ghalamkarpour, Arash" uniqKey="Ghalamkarpour A" first="Arash" last="Ghalamkarpour">Arash Ghalamkarpour</name><affiliation><inist:fA14 i1="03"><s1>Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain</s1><s2>1200 Brussels</s2><s3>BEL</s3><sZ>3 aut.</sZ><sZ>9 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Onoufriadis, Alexandros" sort="Onoufriadis, Alexandros" uniqKey="Onoufriadis A" first="Alexandros" last="Onoufriadis">Alexandros Onoufriadis</name><affiliation><inist:fA14 i1="02"><s1>Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital</s1><s2>London SE1 9RT</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ></inist:fA14></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><inist:fA14 i1="09"><s1>Lymphatic Development Laboratory, Cancer Research UK London Research Institute</s1><s2>London WC2A 3PX</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Devery, Sophie" sort="Devery, Sophie" uniqKey="Devery S" first="Sophie" last="Devery">Sophie Devery</name><affiliation><inist:fA14 i1="10"><s1>Moorfields Eye Hospital NHS Foundation Trust</s1><s2>London EC1V 2PD</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14></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><inist:fA14 i1="11"><s1>C. Hooft Children's Hospital, Ghent University Hospital</s1><s2>9000 Ghent</s2><s3>BEL</s3><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Laer, Lut Van" sort="Laer, Lut Van" uniqKey="Laer L" first="Lut Van" last="Laer">Lut Van Laer</name><affiliation><inist:fA14 i1="08"><s1>Center for Medical Genetics, Antwerp University Hospital and University of Antwerp</s1><s2>2650 Antwerp</s2><s3>BEL</s3><sZ>8 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Singer, Amihood" sort="Singer, Amihood" uniqKey="Singer A" first="Amihood" last="Singer">Amihood Singer</name><affiliation><inist:fA14 i1="12"><s1>Paediatrics and Medical Genetics, Barzilai Medical Center</s1><s2>78306 Ashkelon</s2><s3>ISR</s3><sZ>15 aut.</sZ></inist:fA14></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><inist:fA14 i1="13"><s1>Division of Medical Genetics, North Shore-Long Island Jewish Health System</s1><s2>Manhasset, NY 11030</s2><s3>USA</s3><sZ>16 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mcentagart, Meriel" sort="Mcentagart, Meriel" uniqKey="Mcentagart M" first="Meriel" last="Mcentagart">Meriel Mcentagart</name><affiliation><inist:fA14 i1="14"><s1>South West Thames Regional Genetics Service, St. George's University of London</s1><s2>London SW17 ORE</s2><s3>GBR</s3><sZ>17 aut.</sZ><sZ>19 aut.</sZ><sZ>25 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Quarrell, Oliver" sort="Quarrell, Oliver" uniqKey="Quarrell O" first="Oliver" last="Quarrell">Oliver Quarrell</name><affiliation><inist:fA14 i1="15"><s1>Sheffield Clinical Genetics Service, Sheffield Children's Hospital</s1><s2>Sheffield S10 2TH</s2><s3>GBR</s3><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Brice, Glen" sort="Brice, Glen" uniqKey="Brice G" first="Glen" last="Brice">Glen Brice</name><affiliation><inist:fA14 i1="14"><s1>South West Thames Regional Genetics Service, St. George's University of London</s1><s2>London SW17 ORE</s2><s3>GBR</s3><sZ>17 aut.</sZ><sZ>19 aut.</sZ><sZ>25 aut.</sZ></inist:fA14></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><inist:fA14 i1="02"><s1>Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital</s1><s2>London SE1 9RT</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ></inist:fA14></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><inist:fA14 i1="06"><s1>Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht</s1><s2>3584 CT Utrecht</s2><s3>NLD</s3><sZ>6 aut.</sZ><sZ>21 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Makinen, Taija" sort="Makinen, Taija" uniqKey="Makinen T" first="Taija" last="Makinen">Taija Makinen</name><affiliation><inist:fA14 i1="09"><s1>Lymphatic Development Laboratory, Cancer Research UK London Research Institute</s1><s2>London WC2A 3PX</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Vikkula, Miikka" sort="Vikkula, Miikka" uniqKey="Vikkula M" first="Miikka" last="Vikkula">Miikka Vikkula</name><affiliation><inist:fA14 i1="03"><s1>Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain</s1><s2>1200 Brussels</s2><s3>BEL</s3><sZ>3 aut.</sZ><sZ>9 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="16"><s1>Walloon Excellence in Lifesciences and Biotechnology, Université catholique de Louvain</s1><s2>1200 Brussels</s2><s3>BEL</s3><sZ>23 aut.</sZ></inist:fA14></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><inist:fA14 i1="17"><s1>Department of Cardiac and Vascular Sciences, St. George's University of London</s1><s2>London SW17 0RE</s2><s3>GBR</s3><sZ>24 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mansour, Sahar" sort="Mansour, Sahar" uniqKey="Mansour S" first="Sahar" last="Mansour">Sahar Mansour</name><affiliation><inist:fA14 i1="14"><s1>South West Thames Regional Genetics Service, St. George's University of London</s1><s2>London SW17 ORE</s2><s3>GBR</s3><sZ>17 aut.</sZ><sZ>19 aut.</sZ><sZ>25 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Jeffery, Steve" sort="Jeffery, Steve" uniqKey="Jeffery S" first="Steve" last="Jeffery">Steve Jeffery</name><affiliation><inist:fA14 i1="01"><s1>Medical Genetics Unit, Biomedical Sciences, St. George's University of London</s1><s2>London SW17 0RE</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>26 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">American journal of human genetics</title><title level="j" type="abbreviated">Am. j. hum. genet.</title><idno type="ISSN">0002-9297</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">American journal of human genetics</title><title level="j" type="abbreviated">Am. j. hum. genet.</title><idno type="ISSN">0002-9297</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Autosomal character</term><term>Chorioretinopathy</term><term>Congenital</term><term>Dominant character</term><term>Genetic disease</term><term>Genetics</term><term>Human</term><term>Lymphedema</term><term>Microcephaly</term><term>Mutation</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Microcéphalie</term><term>Lymphoedème</term><term>Choriorétinopathie</term><term>Mutation</term><term>Maladie héréditaire</term><term>Caractère autosomique</term><term>Caractère dominant</term><term>Congénital</term><term>Génétique</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 KIFI11 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.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0002-9297</s0></fA01><fA02 i1="01"><s0>AJHGAG</s0></fA02><fA03 i2="1"><s0>Am. j. hum. genet.</s0></fA03><fA05><s2>90</s2></fA05><fA06><s2>2</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy</s1></fA08><fA11 i1="01" i2="1"><s1>OSTERGAARD (Pia)</s1></fA11><fA11 i1="02" i2="1"><s1>SIMPSON (Michael A.)</s1></fA11><fA11 i1="03" i2="1"><s1>MENDOLA (Antonella)</s1></fA11><fA11 i1="04" i2="1"><s1>VASUDEVAN (Pradeep)</s1></fA11><fA11 i1="05" i2="1"><s1>CONNELL (Fiona C.)</s1></fA11><fA11 i1="06" i2="1"><s1>IMPEL (Andreas Van)</s1></fA11><fA11 i1="07" i2="1"><s1>MOORE (Anthony T.)</s1></fA11><fA11 i1="08" i2="1"><s1>LOEYS (Bart L.)</s1></fA11><fA11 i1="09" i2="1"><s1>GHALAMKARPOUR (Arash)</s1></fA11><fA11 i1="10" i2="1"><s1>ONOUFRIADIS (Alexandros)</s1></fA11><fA11 i1="11" i2="1"><s1>MARTINEZ-CORRAL (Ines)</s1></fA11><fA11 i1="12" i2="1"><s1>DEVERY (Sophie)</s1></fA11><fA11 i1="13" i2="1"><s1>LEROY (Jules G.)</s1></fA11><fA11 i1="14" i2="1"><s1>LAER (Lut Van)</s1></fA11><fA11 i1="15" i2="1"><s1>SINGER (Amihood)</s1></fA11><fA11 i1="16" i2="1"><s1>BIALER (Martin G.)</s1></fA11><fA11 i1="17" i2="1"><s1>MCENTAGART (Meriel)</s1></fA11><fA11 i1="18" i2="1"><s1>QUARRELL (Oliver)</s1></fA11><fA11 i1="19" i2="1"><s1>BRICE (Glen)</s1></fA11><fA11 i1="20" i2="1"><s1>TREMBATH (Richard C.)</s1></fA11><fA11 i1="21" i2="1"><s1>SCHULTE-MERKER (Stefan)</s1></fA11><fA11 i1="22" i2="1"><s1>MAKINEN (Taija)</s1></fA11><fA11 i1="23" i2="1"><s1>VIKKULA (Miikka)</s1></fA11><fA11 i1="24" i2="1"><s1>MORTIMER (Peter S.)</s1></fA11><fA11 i1="25" i2="1"><s1>MANSOUR (Sahar)</s1></fA11><fA11 i1="26" i2="1"><s1>JEFFERY (Steve)</s1></fA11><fA14 i1="01"><s1>Medical Genetics Unit, Biomedical Sciences, St. George's University of London</s1><s2>London SW17 0RE</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>26 aut.</sZ></fA14><fA14 i1="02"><s1>Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital</s1><s2>London SE1 9RT</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ></fA14><fA14 i1="03"><s1>Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain</s1><s2>1200 Brussels</s2><s3>BEL</s3><sZ>3 aut.</sZ><sZ>9 aut.</sZ><sZ>23 aut.</sZ></fA14><fA14 i1="04"><s1>Clinical Genetics, University Hospitals of Leicester National Health Services Trust, Leicester Royal Infirmary</s1><s2>Leicester LE1 5WW</s2><s3>GBR</s3><sZ>4 aut.</sZ></fA14><fA14 i1="05"><s1>Clinical Genetics, Guy's and St. Thomas' National Health Services Foundation Trust, Guy's Hospital</s1><s2>London SE1 9RT</s2><s3>GBR</s3><sZ>5 aut.</sZ></fA14><fA14 i1="06"><s1>Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht</s1><s2>3584 CT Utrecht</s2><s3>NLD</s3><sZ>6 aut.</sZ><sZ>21 aut.</sZ></fA14><fA14 i1="07"><s1>University College London Institute of Ophthalmology, Moorfields Eye Hospital and Hospital for Children</s1><s2>London EC1V 2PD</s2><s3>GBR</s3><sZ>7 aut.</sZ></fA14><fA14 i1="08"><s1>Center for Medical Genetics, Antwerp University Hospital and University of Antwerp</s1><s2>2650 Antwerp</s2><s3>BEL</s3><sZ>8 aut.</sZ><sZ>14 aut.</sZ></fA14><fA14 i1="09"><s1>Lymphatic Development Laboratory, Cancer Research UK London Research Institute</s1><s2>London WC2A 3PX</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>22 aut.</sZ></fA14><fA14 i1="10"><s1>Moorfields Eye Hospital NHS Foundation Trust</s1><s2>London EC1V 2PD</s2><s3>GBR</s3><sZ>12 aut.</sZ></fA14><fA14 i1="11"><s1>C. Hooft Children's Hospital, Ghent University Hospital</s1><s2>9000 Ghent</s2><s3>BEL</s3><sZ>13 aut.</sZ></fA14><fA14 i1="12"><s1>Paediatrics and Medical Genetics, Barzilai Medical Center</s1><s2>78306 Ashkelon</s2><s3>ISR</s3><sZ>15 aut.</sZ></fA14><fA14 i1="13"><s1>Division of Medical Genetics, North Shore-Long Island Jewish Health System</s1><s2>Manhasset, NY 11030</s2><s3>USA</s3><sZ>16 aut.</sZ></fA14><fA14 i1="14"><s1>South West Thames Regional Genetics Service, St. George's University of London</s1><s2>London SW17 ORE</s2><s3>GBR</s3><sZ>17 aut.</sZ><sZ>19 aut.</sZ><sZ>25 aut.</sZ></fA14><fA14 i1="15"><s1>Sheffield Clinical Genetics Service, Sheffield Children's Hospital</s1><s2>Sheffield S10 2TH</s2><s3>GBR</s3><sZ>18 aut.</sZ></fA14><fA14 i1="16"><s1>Walloon Excellence in Lifesciences and Biotechnology, Université catholique de Louvain</s1><s2>1200 Brussels</s2><s3>BEL</s3><sZ>23 aut.</sZ></fA14><fA14 i1="17"><s1>Department of Cardiac and Vascular Sciences, St. George's University of London</s1><s2>London SW17 0RE</s2><s3>GBR</s3><sZ>24 aut.</sZ></fA14><fA20><s1>356-362</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>2610</s2><s5>354000509256020180</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>24 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0150136</s0></fA47><fA60><s1>P</s1><s3>C</s3></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>American journal of human genetics</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>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 KIFI11 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.</s0></fC01><fC02 i1="01" i2="X"><s0>002A04</s0></fC02><fC02 i1="02" i2="X"><s0>002A07</s0></fC02><fC02 i1="03" i2="X"><s0>002B23A</s0></fC02><fC02 i1="04" i2="X"><s0>002B17D</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Microcéphalie</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Microcephaly</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Microcefalia</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Lymphoedème</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Lymphedema</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Linfedema</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Choriorétinopathie</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Chorioretinopathy</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Coriorretinopatía</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Mutation</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Mutation</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Mutación</s0><s5>09</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Maladie héréditaire</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Genetic disease</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Enfermedad hereditaria</s0><s5>10</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Caractère autosomique</s0><s5>11</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Autosomal character</s0><s5>11</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Carácter autosómico</s0><s5>11</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Caractère dominant</s0><s5>12</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Dominant character</s0><s5>12</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Carácter dominante</s0><s5>12</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Congénital</s0><s5>13</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Congenital</s0><s5>13</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Congénito</s0><s5>13</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Génétique</s0><s5>14</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Genetics</s0><s5>14</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Genética</s0><s5>14</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Homme</s0><s5>15</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Human</s0><s5>15</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Hombre</s0><s5>15</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Maladie congénitale</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Congenital disease</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Enfermedad congénita</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Malformation</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Malformation</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Malformación</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>41</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Pathologie de l'appareil circulatoire</s0><s5>42</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Cardiovascular disease</s0><s5>42</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Aparato circulatorio patología</s0><s5>42</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Pathologie des vaisseaux lymphatiques</s0><s5>43</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Lymphatic vessel disease</s0><s5>43</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Linfático patología</s0><s5>43</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Pathologie de l'oeil</s0><s5>44</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Eye disease</s0><s5>44</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Ojo patología</s0><s5>44</s5></fC07><fC07 i1="09" i2="X" l="FRE"><s0>Rétinopathie</s0><s5>45</s5></fC07><fC07 i1="09" i2="X" l="ENG"><s0>Retinopathy</s0><s5>45</s5></fC07><fC07 i1="09" i2="X" l="SPA"><s0>Retinopatía</s0><s5>45</s5></fC07><fC07 i1="10" i2="X" l="FRE"><s0>Pathologie de l'uvée</s0><s5>46</s5></fC07><fC07 i1="10" i2="X" l="ENG"><s0>Uvea disease</s0><s5>46</s5></fC07><fC07 i1="10" i2="X" l="SPA"><s0>Uvea patología</s0><s5>46</s5></fC07><fN21><s1>114</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard><server><NO>PASCAL 12-0150136 INIST</NO><ET>Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy</ET><AU>OSTERGAARD (Pia); SIMPSON (Michael A.); MENDOLA (Antonella); VASUDEVAN (Pradeep); CONNELL (Fiona C.); IMPEL (Andreas Van); MOORE (Anthony T.); LOEYS (Bart L.); GHALAMKARPOUR (Arash); ONOUFRIADIS (Alexandros); MARTINEZ-CORRAL (Ines); DEVERY (Sophie); LEROY (Jules G.); LAER (Lut Van); SINGER (Amihood); BIALER (Martin G.); MCENTAGART (Meriel); QUARRELL (Oliver); BRICE (Glen); TREMBATH (Richard C.); SCHULTE-MERKER (Stefan); MAKINEN (Taija); VIKKULA (Miikka); MORTIMER (Peter S.); MANSOUR (Sahar); JEFFERY (Steve)</AU><AF>Medical Genetics Unit, Biomedical Sciences, St. George's University of London/London SW17 0RE/Royaume-Uni (1 aut., 26 aut.); Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital/London SE1 9RT/Royaume-Uni (2 aut., 10 aut., 20 aut.); Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain/1200 Brussels/Belgique (3 aut., 9 aut., 23 aut.); Clinical Genetics, University Hospitals of Leicester National Health Services Trust, Leicester Royal Infirmary/Leicester LE1 5WW/Royaume-Uni (4 aut.); Clinical Genetics, Guy's and St. Thomas' National Health Services Foundation Trust, Guy's Hospital/London SE1 9RT/Royaume-Uni (5 aut.); Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, in collaboration with the Universitair Medisch Centrum Utrecht/3584 CT Utrecht/Pays-Bas (6 aut., 21 aut.); University College London Institute of Ophthalmology, Moorfields Eye Hospital and Hospital for Children/London EC1V 2PD/Royaume-Uni (7 aut.); Center for Medical Genetics, Antwerp University Hospital and University of Antwerp/2650 Antwerp/Belgique (8 aut., 14 aut.); Lymphatic Development Laboratory, Cancer Research UK London Research Institute/London WC2A 3PX/Royaume-Uni (11 aut., 22 aut.); Moorfields Eye Hospital NHS Foundation Trust/London EC1V 2PD/Royaume-Uni (12 aut.); C. Hooft Children's Hospital, Ghent University Hospital/9000 Ghent/Belgique (13 aut.); Paediatrics and Medical Genetics, Barzilai Medical Center/78306 Ashkelon/Israël (15 aut.); Division of Medical Genetics, North Shore-Long Island Jewish Health System/Manhasset, NY 11030/Etats-Unis (16 aut.); South West Thames Regional Genetics Service, St. George's University of London/London SW17 ORE/Royaume-Uni (17 aut., 19 aut., 25 aut.); Sheffield Clinical Genetics Service, Sheffield Children's Hospital/Sheffield S10 2TH/Royaume-Uni (18 aut.); Walloon Excellence in Lifesciences and Biotechnology, Université catholique de Louvain/1200 Brussels/Belgique (23 aut.); Department of Cardiac and Vascular Sciences, St. George's University of London/London SW17 0RE/Royaume-Uni (24 aut.)</AF><DT>Publication en série; Compte-rendu; Niveau analytique</DT><SO>American journal of human genetics; ISSN 0002-9297; Coden AJHGAG; Etats-Unis; Da. 2012; Vol. 90; No. 2; Pp. 356-362; Bibl. 24 ref.</SO><LA>Anglais</LA><EA>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 KIFI11 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.</EA><CC>002A04; 002A07; 002B23A; 002B17D</CC><FD>Microcéphalie; Lymphoedème; Choriorétinopathie; Mutation; Maladie héréditaire; Caractère autosomique; Caractère dominant; Congénital; Génétique; Homme</FD><FG>Pathologie de l'encéphale; Maladie congénitale; Malformation; Pathologie du système nerveux central; Pathologie du système nerveux; Pathologie de l'appareil circulatoire; Pathologie des vaisseaux lymphatiques; Pathologie de l'oeil; Rétinopathie; Pathologie de l'uvée</FG><ED>Microcephaly; Lymphedema; Chorioretinopathy; Mutation; Genetic disease; Autosomal character; Dominant character; Congenital; Genetics; Human</ED><EG>Cerebral disorder; Congenital disease; Malformation; Central nervous system disease; Nervous system diseases; Cardiovascular disease; Lymphatic vessel disease; Eye disease; Retinopathy; Uvea disease</EG><SD>Microcefalia; Linfedema; Coriorretinopatía; Mutación; Enfermedad hereditaria; Carácter autosómico; Carácter dominante; Congénito; Genética; Hombre</SD><LO>INIST-2610.354000509256020180</LO><ID>12-0150136</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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