Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement
Identifieur interne : 000397 ( Main/Exploration ); précédent : 000396; suivant : 000398Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement
Auteurs : Miriam Schmidts [Royaume-Uni] ; Heleen H. Arts [Pays-Bas] ; Ernie M H F. Bongers [Pays-Bas] ; Zhimin Yap [Royaume-Uni] ; Machteld M. Oud [Pays-Bas] ; Dinu Antony [Royaume-Uni] ; Lonneke Duijkers [Pays-Bas] ; Richard D. Emes [Royaume-Uni] ; Jim Stalker [Royaume-Uni] ; Jan-Bart L. Yntema [Pays-Bas] ; Vincent Plagnol [Royaume-Uni] ; Alexander Hoischen [Pays-Bas] ; Christian Gilissen [Pays-Bas] ; Elisabeth Forsythe [Royaume-Uni] ; Ekkehart Lausch [Allemagne] ; Joris A. Veltman [Pays-Bas] ; Nel Roeleveld [Pays-Bas] ; Andrea Superti-Furga [Suisse] ; Anna Kutkowska-Kazmierczak [Pologne] ; Erik-Jan Kamsteeg [Pays-Bas] ; Nursel Elçio Lu [Turquie] ; Merel C. Van Maarle [Pays-Bas] ; Luitgard M. Graul-Neumann [Allemagne] ; Koenraad Devriendt [Belgique] ; Sarah F. Smithson [Royaume-Uni] ; Diana Wellesley [Royaume-Uni] ; Nienke E. Verbeek [Pays-Bas] ; Raoul C M. Hennekam [Pays-Bas] ; Hulya Kayserili [Turquie] ; Peter J. Scambler [Royaume-Uni] ; Philip L. Beales [Royaume-Uni] ; Nine Vam Knoers [Pays-Bas] ; Ronald Roepman [Pays-Bas] ; Hannah M. Mitchison [Royaume-Uni]Source :
- Journal of Medical Genetics [ 0022-2593 ] ; 2013-05.
Abstract
Background Jeune asphyxiating thoracic dystrophy (JATD) is a rare, often lethal, recessively inherited chondrodysplasia characterised by shortened ribs and long bones, sometimes accompanied by polydactyly, and renal, liver and retinal disease. Mutations in intraflagellar transport (IFT) genes cause JATD, including the IFT dynein-2 motor subunit gene DYNC2H1. Genetic heterogeneity and the large DYNC2H1 gene size have hindered JATD genetic diagnosis. Aims and methods To determine the contribution to JATD we screened DYNC2H1 in 71 JATD patients JATD patients combining SNP mapping, Sanger sequencing and exome sequencing. Results and conclusions We detected 34 DYNC2H1 mutations in 29/71 (41%) patients from 19/57 families (33%), showing it as a major cause of JATD especially in Northern European patients. This included 13 early protein termination mutations (nonsense/frameshift, deletion, splice site) but no patients carried these in combination, suggesting the human phenotype is at least partly hypomorphic. In addition, 21 missense mutations were distributed across DYNC2H1 and these showed some clustering to functional domains, especially the ATP motor domain. DYNC2H1 patients largely lacked significant extra-skeletal involvement, demonstrating an important genotype–phenotype correlation in JATD. Significant variability exists in the course and severity of the thoracic phenotype, both between affected siblings with identical DYNC2H1 alleles and among individuals with different alleles, which suggests the DYNC2H1 phenotype might be subject to modifier alleles, non-genetic or epigenetic factors. Assessment of fibroblasts from patients showed accumulation of anterograde IFT proteins in the ciliary tips, confirming defects similar to patients with other retrograde IFT machinery mutations, which may be of undervalued potential for diagnostic purposes.
Url:
DOI: 10.1136/jmedgenet-2012-101284
Affiliations:
- Allemagne, Belgique, Pays-Bas, Pologne, Royaume-Uni, Suisse, Turquie
- Angleterre, Bade-Wurtemberg, Berlin, Canton de Vaud, District de Fribourg-en-Brisgau, Grand Londres, Gueldre, Hollande-Méridionale, Hollande-Septentrionale, Nottinghamshire, Utrecht (province)
- Amsterdam, Berlin, Fribourg-en-Brisgau, Lausanne, Leyde, Londres, Nimègue, Nottingham, Utrecht
- University College de Londres, Université de Nottingham
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000C14
- to stream Istex, to step Curation: 000C13
- to stream Istex, to step Checkpoint: 000053
- to stream Main, to step Merge: 000397
- to stream Main, to step Curation: 000397
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement</title><author><name sortKey="Schmidts, Miriam" sort="Schmidts, Miriam" uniqKey="Schmidts M" first="Miriam" last="Schmidts">Miriam Schmidts</name></author><author><name sortKey="Arts, Heleen H" sort="Arts, Heleen H" uniqKey="Arts H" first="Heleen H" last="Arts">Heleen H. Arts</name></author><author><name sortKey="Bongers, Ernie M H F" sort="Bongers, Ernie M H F" uniqKey="Bongers E" first="Ernie M H F" last="Bongers">Ernie M H F. Bongers</name></author><author><name sortKey="Yap, Zhimin" sort="Yap, Zhimin" uniqKey="Yap Z" first="Zhimin" last="Yap">Zhimin Yap</name></author><author><name sortKey="Oud, Machteld M" sort="Oud, Machteld M" uniqKey="Oud M" first="Machteld M" last="Oud">Machteld M. Oud</name></author><author><name sortKey="Antony, Dinu" sort="Antony, Dinu" uniqKey="Antony D" first="Dinu" last="Antony">Dinu Antony</name></author><author><name sortKey="Duijkers, Lonneke" sort="Duijkers, Lonneke" uniqKey="Duijkers L" first="Lonneke" last="Duijkers">Lonneke Duijkers</name></author><author><name sortKey="Emes, Richard D" sort="Emes, Richard D" uniqKey="Emes R" first="Richard D" last="Emes">Richard D. Emes</name></author><author><name sortKey="Stalker, Jim" sort="Stalker, Jim" uniqKey="Stalker J" first="Jim" last="Stalker">Jim Stalker</name></author><author><name sortKey="Yntema, Jan Bart L" sort="Yntema, Jan Bart L" uniqKey="Yntema J" first="Jan-Bart L" last="Yntema">Jan-Bart L. Yntema</name></author><author><name sortKey="Plagnol, Vincent" sort="Plagnol, Vincent" uniqKey="Plagnol V" first="Vincent" last="Plagnol">Vincent Plagnol</name></author><author><name sortKey="Hoischen, Alexander" sort="Hoischen, Alexander" uniqKey="Hoischen A" first="Alexander" last="Hoischen">Alexander Hoischen</name></author><author><name sortKey="Gilissen, Christian" sort="Gilissen, Christian" uniqKey="Gilissen C" first="Christian" last="Gilissen">Christian Gilissen</name></author><author><name sortKey="Forsythe, Elisabeth" sort="Forsythe, Elisabeth" uniqKey="Forsythe E" first="Elisabeth" last="Forsythe">Elisabeth Forsythe</name></author><author><name sortKey="Lausch, Ekkehart" sort="Lausch, Ekkehart" uniqKey="Lausch E" first="Ekkehart" last="Lausch">Ekkehart Lausch</name></author><author><name sortKey="Veltman, Joris A" sort="Veltman, Joris A" uniqKey="Veltman J" first="Joris A" last="Veltman">Joris A. Veltman</name></author><author><name sortKey="Roeleveld, Nel" sort="Roeleveld, Nel" uniqKey="Roeleveld N" first="Nel" last="Roeleveld">Nel Roeleveld</name></author><author><name sortKey="Superti Furga, Andrea" sort="Superti Furga, Andrea" uniqKey="Superti Furga A" first="Andrea" last="Superti-Furga">Andrea Superti-Furga</name></author><author><name sortKey="Kutkowska Kazmierczak, Anna" sort="Kutkowska Kazmierczak, Anna" uniqKey="Kutkowska Kazmierczak A" first="Anna" last="Kutkowska-Kazmierczak">Anna Kutkowska-Kazmierczak</name></author><author><name sortKey="Kamsteeg, Erik Jan" sort="Kamsteeg, Erik Jan" uniqKey="Kamsteeg E" first="Erik-Jan" last="Kamsteeg">Erik-Jan Kamsteeg</name></author><author><name sortKey="Elcio Lu, Nursel" sort="Elcio Lu, Nursel" uniqKey="Elcio Lu N" first="Nursel" last="Elçio Lu">Nursel Elçio Lu</name></author><author><name sortKey="Van Maarle, Merel C" sort="Van Maarle, Merel C" uniqKey="Van Maarle M" first="Merel C" last="Van Maarle">Merel C. Van Maarle</name></author><author><name sortKey="Graul Neumann, Luitgard M" sort="Graul Neumann, Luitgard M" uniqKey="Graul Neumann L" first="Luitgard M" last="Graul-Neumann">Luitgard M. Graul-Neumann</name></author><author><name sortKey="Devriendt, Koenraad" sort="Devriendt, Koenraad" uniqKey="Devriendt K" first="Koenraad" last="Devriendt">Koenraad Devriendt</name></author><author><name sortKey="Smithson, Sarah F" sort="Smithson, Sarah F" uniqKey="Smithson S" first="Sarah F" last="Smithson">Sarah F. Smithson</name></author><author><name sortKey="Wellesley, Diana" sort="Wellesley, Diana" uniqKey="Wellesley D" first="Diana" last="Wellesley">Diana Wellesley</name></author><author><name sortKey="Verbeek, Nienke E" sort="Verbeek, Nienke E" uniqKey="Verbeek N" first="Nienke E" last="Verbeek">Nienke E. Verbeek</name></author><author><name sortKey="Hennekam, Raoul C M" sort="Hennekam, Raoul C M" uniqKey="Hennekam R" first="Raoul C M" last="Hennekam">Raoul C M. Hennekam</name></author><author><name sortKey="Kayserili, Hulya" sort="Kayserili, Hulya" uniqKey="Kayserili H" first="Hulya" last="Kayserili">Hulya Kayserili</name></author><author><name sortKey="Scambler, Peter J" sort="Scambler, Peter J" uniqKey="Scambler P" first="Peter J" last="Scambler">Peter J. Scambler</name></author><author><name sortKey="Beales, Philip L" sort="Beales, Philip L" uniqKey="Beales P" first="Philip L" last="Beales">Philip L. Beales</name></author><author><name sortKey="Knoers, Nine Vam" sort="Knoers, Nine Vam" uniqKey="Knoers N" first="Nine Vam" last="Knoers">Nine Vam Knoers</name></author><author><name sortKey="Roepman, Ronald" sort="Roepman, Ronald" uniqKey="Roepman R" first="Ronald" last="Roepman">Ronald Roepman</name></author><author><name sortKey="Mitchison, Hannah M" sort="Mitchison, Hannah M" uniqKey="Mitchison H" first="Hannah M" last="Mitchison">Hannah M. Mitchison</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:EFE630C08BA484FCC659095E33A3C3349589E1E3</idno><date when="2013" year="2013">2013</date><idno type="doi">10.1136/jmedgenet-2012-101284</idno><idno type="url">https://api.istex.fr/document/EFE630C08BA484FCC659095E33A3C3349589E1E3/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000C14</idno><idno type="wicri:Area/Istex/Curation">000C13</idno><idno type="wicri:Area/Istex/Checkpoint">000053</idno><idno type="wicri:doubleKey">0022-2593:2013:Schmidts M:exome:sequencing:identifies</idno><idno type="wicri:Area/Main/Merge">000397</idno><idno type="wicri:Area/Main/Curation">000397</idno><idno type="wicri:Area/Main/Exploration">000397</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement</title><author><name sortKey="Schmidts, Miriam" sort="Schmidts, Miriam" uniqKey="Schmidts M" first="Miriam" last="Schmidts">Miriam Schmidts</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Molecular Medicine Unit, Birth Defects Research Centre, University College London (UCL) Institute of Child Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Arts, Heleen H" sort="Arts, Heleen H" uniqKey="Arts H" first="Heleen H" last="Arts">Heleen H. Arts</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Institute for Genetic and Metabolic Disease, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Bongers, Ernie M H F" sort="Bongers, Ernie M H F" uniqKey="Bongers E" first="Ernie M H F" last="Bongers">Ernie M H F. Bongers</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Institute for Genetic and Metabolic Disease, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Yap, Zhimin" sort="Yap, Zhimin" uniqKey="Yap Z" first="Zhimin" last="Yap">Zhimin Yap</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Molecular Medicine Unit, Birth Defects Research Centre, University College London (UCL) Institute of Child Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Oud, Machteld M" sort="Oud, Machteld M" uniqKey="Oud M" first="Machteld M" last="Oud">Machteld M. Oud</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Institute for Genetic and Metabolic Disease, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Antony, Dinu" sort="Antony, Dinu" uniqKey="Antony D" first="Dinu" last="Antony">Dinu Antony</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Molecular Medicine Unit, Birth Defects Research Centre, University College London (UCL) Institute of Child Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Duijkers, Lonneke" sort="Duijkers, Lonneke" uniqKey="Duijkers L" first="Lonneke" last="Duijkers">Lonneke Duijkers</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Physiology, Radboud University Medical Centre Nijmegen, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Emes, Richard D" sort="Emes, Richard D" uniqKey="Emes R" first="Richard D" last="Emes">Richard D. Emes</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Veterinary Medicine and Science, University of Nottingham, Nottingham, Leicestershire</wicri:regionArea><orgName type="university">Université de Nottingham</orgName><placeName><settlement type="city">Nottingham</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Nottinghamshire</region></placeName></affiliation></author><author><name sortKey="Stalker, Jim" sort="Stalker, Jim" uniqKey="Stalker J" first="Jim" last="Stalker">Jim Stalker</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea><wicri:noRegion>Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Yntema, Jan Bart L" sort="Yntema, Jan Bart L" uniqKey="Yntema J" first="Jan-Bart L" last="Yntema">Jan-Bart L. Yntema</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Paediatrics, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Plagnol, Vincent" sort="Plagnol, Vincent" uniqKey="Plagnol V" first="Vincent" last="Plagnol">Vincent Plagnol</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Genetics, Environment and Evolution, UCL Genetics Institute (UGI), University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Hoischen, Alexander" sort="Hoischen, Alexander" uniqKey="Hoischen A" first="Alexander" last="Hoischen">Alexander Hoischen</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Institute for Genetic and Metabolic Disease, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Gilissen, Christian" sort="Gilissen, Christian" uniqKey="Gilissen C" first="Christian" last="Gilissen">Christian Gilissen</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Institute for Genetic and Metabolic Disease, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Forsythe, Elisabeth" sort="Forsythe, Elisabeth" uniqKey="Forsythe E" first="Elisabeth" last="Forsythe">Elisabeth Forsythe</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Molecular Medicine Unit, Birth Defects Research Centre, University College London (UCL) Institute of Child Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Lausch, Ekkehart" sort="Lausch, Ekkehart" uniqKey="Lausch E" first="Ekkehart" last="Lausch">Ekkehart Lausch</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Pediatric Genetics, Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Veltman, Joris A" sort="Veltman, Joris A" uniqKey="Veltman J" first="Joris A" last="Veltman">Joris A. Veltman</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Institute for Genetic and Metabolic Disease, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Roeleveld, Nel" sort="Roeleveld, Nel" uniqKey="Roeleveld N" first="Nel" last="Roeleveld">Nel Roeleveld</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Institute for Genetic and Metabolic Disease, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Biostatistics and HTA, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Evidence Based Practice, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Superti Furga, Andrea" sort="Superti Furga, Andrea" uniqKey="Superti Furga A" first="Andrea" last="Superti-Furga">Andrea Superti-Furga</name><affiliation wicri:level="3"><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Pediatrics, Lausanne University Hospital and University of Lausanne, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Kutkowska Kazmierczak, Anna" sort="Kutkowska Kazmierczak, Anna" uniqKey="Kutkowska Kazmierczak A" first="Anna" last="Kutkowska-Kazmierczak">Anna Kutkowska-Kazmierczak</name><affiliation wicri:level="1"><country xml:lang="fr">Pologne</country><wicri:regionArea>Department of Medical Genetics, Institute of Mother and Child, Warsaw</wicri:regionArea><wicri:noRegion>Warsaw</wicri:noRegion></affiliation></author><author><name sortKey="Kamsteeg, Erik Jan" sort="Kamsteeg, Erik Jan" uniqKey="Kamsteeg E" first="Erik-Jan" last="Kamsteeg">Erik-Jan Kamsteeg</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Institute for Genetic and Metabolic Disease, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Elcio Lu, Nursel" sort="Elcio Lu, Nursel" uniqKey="Elcio Lu N" first="Nursel" last="Elçio Lu">Nursel Elçio Lu</name><affiliation wicri:level="1"><country xml:lang="fr">Turquie</country><wicri:regionArea>Department of Pediatric Genetics, Marmara University Hospital, Istanbul</wicri:regionArea><wicri:noRegion>Istanbul</wicri:noRegion></affiliation></author><author><name sortKey="Van Maarle, Merel C" sort="Van Maarle, Merel C" uniqKey="Van Maarle M" first="Merel C" last="Van Maarle">Merel C. Van Maarle</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Clinical Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Graul Neumann, Luitgard M" sort="Graul Neumann, Luitgard M" uniqKey="Graul Neumann L" first="Luitgard M" last="Graul-Neumann">Luitgard M. Graul-Neumann</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Medical Genetics and Human Genetics, University Hospital Charité, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Devriendt, Koenraad" sort="Devriendt, Koenraad" uniqKey="Devriendt K" first="Koenraad" last="Devriendt">Koenraad Devriendt</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory for Genetics of Human Development, Department of Human Genetics, KU Leuven University, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Smithson, Sarah F" sort="Smithson, Sarah F" uniqKey="Smithson S" first="Sarah F" last="Smithson">Sarah F. Smithson</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Clinical Genetics, St. Michael's Hospital, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Wellesley, Diana" sort="Wellesley, Diana" uniqKey="Wellesley D" first="Diana" last="Wellesley">Diana Wellesley</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Medicine, University of Southampton and Essex Clinical Genetics Service, Princess Anne Hospital, Southampton</wicri:regionArea><wicri:noRegion>Southampton</wicri:noRegion></affiliation></author><author><name sortKey="Verbeek, Nienke E" sort="Verbeek, Nienke E" uniqKey="Verbeek N" first="Nienke E" last="Verbeek">Nienke E. Verbeek</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Genetics, University Medical Centre Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Hennekam, Raoul C M" sort="Hennekam, Raoul C M" uniqKey="Hennekam R" first="Raoul C M" last="Hennekam">Raoul C M. Hennekam</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Kayserili, Hulya" sort="Kayserili, Hulya" uniqKey="Kayserili H" first="Hulya" last="Kayserili">Hulya Kayserili</name><affiliation wicri:level="1"><country xml:lang="fr">Turquie</country><wicri:regionArea>Istanbul Medical Faculty, Medical Genetics Department, Istanbul University, Istanbul</wicri:regionArea><wicri:noRegion>Istanbul</wicri:noRegion></affiliation></author><author><name sortKey="Scambler, Peter J" sort="Scambler, Peter J" uniqKey="Scambler P" first="Peter J" last="Scambler">Peter J. Scambler</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Molecular Medicine Unit, Birth Defects Research Centre, University College London (UCL) Institute of Child Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Beales, Philip L" sort="Beales, Philip L" uniqKey="Beales P" first="Philip L" last="Beales">Philip L. Beales</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Molecular Medicine Unit, Birth Defects Research Centre, University College London (UCL) Institute of Child Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Knoers, Nine Vam" sort="Knoers, Nine Vam" uniqKey="Knoers N" first="Nine Vam" last="Knoers">Nine Vam Knoers</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Genetics, University Medical Centre Utrecht, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Roepman, Ronald" sort="Roepman, Ronald" uniqKey="Roepman R" first="Ronald" last="Roepman">Ronald Roepman</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Radboud University Medical Centre, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Institute for Genetic and Metabolic Disease, Radboud University, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Mitchison, Hannah M" sort="Mitchison, Hannah M" uniqKey="Mitchison H" first="Hannah M" last="Mitchison">Hannah M. Mitchison</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Molecular Medicine Unit, Birth Defects Research Centre, University College London (UCL) Institute of Child Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2013-05">2013-05</date><biblScope unit="volume">50</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="309">309</biblScope></imprint><idno type="ISSN">0022-2593</idno></series><idno type="istex">EFE630C08BA484FCC659095E33A3C3349589E1E3</idno><idno type="DOI">10.1136/jmedgenet-2012-101284</idno><idno type="href">jmedgenet-50-309.pdf</idno><idno type="ArticleID">jmedgenet-2012-101284</idno><idno type="PMID">23456818</idno><idno type="Related-article-href">10.1136/jmedgenet-2012-101282</idno><idno type="related-article-ID">RA1</idno><idno type="local">jmedgenet;50/5/309</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Background Jeune asphyxiating thoracic dystrophy (JATD) is a rare, often lethal, recessively inherited chondrodysplasia characterised by shortened ribs and long bones, sometimes accompanied by polydactyly, and renal, liver and retinal disease. Mutations in intraflagellar transport (IFT) genes cause JATD, including the IFT dynein-2 motor subunit gene DYNC2H1. Genetic heterogeneity and the large DYNC2H1 gene size have hindered JATD genetic diagnosis. Aims and methods To determine the contribution to JATD we screened DYNC2H1 in 71 JATD patients JATD patients combining SNP mapping, Sanger sequencing and exome sequencing. Results and conclusions We detected 34 DYNC2H1 mutations in 29/71 (41%) patients from 19/57 families (33%), showing it as a major cause of JATD especially in Northern European patients. This included 13 early protein termination mutations (nonsense/frameshift, deletion, splice site) but no patients carried these in combination, suggesting the human phenotype is at least partly hypomorphic. In addition, 21 missense mutations were distributed across DYNC2H1 and these showed some clustering to functional domains, especially the ATP motor domain. DYNC2H1 patients largely lacked significant extra-skeletal involvement, demonstrating an important genotype–phenotype correlation in JATD. Significant variability exists in the course and severity of the thoracic phenotype, both between affected siblings with identical DYNC2H1 alleles and among individuals with different alleles, which suggests the DYNC2H1 phenotype might be subject to modifier alleles, non-genetic or epigenetic factors. Assessment of fibroblasts from patients showed accumulation of anterograde IFT proteins in the ciliary tips, confirming defects similar to patients with other retrograde IFT machinery mutations, which may be of undervalued potential for diagnostic purposes.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Belgique</li><li>Pays-Bas</li><li>Pologne</li><li>Royaume-Uni</li><li>Suisse</li><li>Turquie</li></country><region><li>Angleterre</li><li>Bade-Wurtemberg</li><li>Berlin</li><li>Canton de Vaud</li><li>District de Fribourg-en-Brisgau</li><li>Grand Londres</li><li>Gueldre</li><li>Hollande-Méridionale</li><li>Hollande-Septentrionale</li><li>Nottinghamshire</li><li>Utrecht (province)</li></region><settlement><li>Amsterdam</li><li>Berlin</li><li>Fribourg-en-Brisgau</li><li>Lausanne</li><li>Leyde</li><li>Londres</li><li>Nimègue</li><li>Nottingham</li><li>Utrecht</li></settlement><orgName><li>University College de Londres</li><li>Université de Nottingham</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Schmidts, Miriam" sort="Schmidts, Miriam" uniqKey="Schmidts M" first="Miriam" last="Schmidts">Miriam Schmidts</name></region><name sortKey="Antony, Dinu" sort="Antony, Dinu" uniqKey="Antony D" first="Dinu" last="Antony">Dinu Antony</name><name sortKey="Beales, Philip L" sort="Beales, Philip L" uniqKey="Beales P" first="Philip L" last="Beales">Philip L. Beales</name><name sortKey="Emes, Richard D" sort="Emes, Richard D" uniqKey="Emes R" first="Richard D" last="Emes">Richard D. Emes</name><name sortKey="Forsythe, Elisabeth" sort="Forsythe, Elisabeth" uniqKey="Forsythe E" first="Elisabeth" last="Forsythe">Elisabeth Forsythe</name><name sortKey="Mitchison, Hannah M" sort="Mitchison, Hannah M" uniqKey="Mitchison H" first="Hannah M" last="Mitchison">Hannah M. Mitchison</name><name sortKey="Plagnol, Vincent" sort="Plagnol, Vincent" uniqKey="Plagnol V" first="Vincent" last="Plagnol">Vincent Plagnol</name><name sortKey="Scambler, Peter J" sort="Scambler, Peter J" uniqKey="Scambler P" first="Peter J" last="Scambler">Peter J. Scambler</name><name sortKey="Smithson, Sarah F" sort="Smithson, Sarah F" uniqKey="Smithson S" first="Sarah F" last="Smithson">Sarah F. Smithson</name><name sortKey="Stalker, Jim" sort="Stalker, Jim" uniqKey="Stalker J" first="Jim" last="Stalker">Jim Stalker</name><name sortKey="Wellesley, Diana" sort="Wellesley, Diana" uniqKey="Wellesley D" first="Diana" last="Wellesley">Diana Wellesley</name><name sortKey="Yap, Zhimin" sort="Yap, Zhimin" uniqKey="Yap Z" first="Zhimin" last="Yap">Zhimin Yap</name></country><country name="Pays-Bas"><region name="Gueldre"><name sortKey="Arts, Heleen H" sort="Arts, Heleen H" uniqKey="Arts H" first="Heleen H" last="Arts">Heleen H. Arts</name></region><name sortKey="Arts, Heleen H" sort="Arts, Heleen H" uniqKey="Arts H" first="Heleen H" last="Arts">Heleen H. Arts</name><name sortKey="Arts, Heleen H" sort="Arts, Heleen H" uniqKey="Arts H" first="Heleen H" last="Arts">Heleen H. Arts</name><name sortKey="Bongers, Ernie M H F" sort="Bongers, Ernie M H F" uniqKey="Bongers E" first="Ernie M H F" last="Bongers">Ernie M H F. Bongers</name><name sortKey="Bongers, Ernie M H F" sort="Bongers, Ernie M H F" uniqKey="Bongers E" first="Ernie M H F" last="Bongers">Ernie M H F. Bongers</name><name sortKey="Bongers, Ernie M H F" sort="Bongers, Ernie M H F" uniqKey="Bongers E" first="Ernie M H F" last="Bongers">Ernie M H F. Bongers</name><name sortKey="Duijkers, Lonneke" sort="Duijkers, Lonneke" uniqKey="Duijkers L" first="Lonneke" last="Duijkers">Lonneke Duijkers</name><name sortKey="Duijkers, Lonneke" sort="Duijkers, Lonneke" uniqKey="Duijkers L" first="Lonneke" last="Duijkers">Lonneke Duijkers</name><name sortKey="Gilissen, Christian" sort="Gilissen, Christian" uniqKey="Gilissen C" first="Christian" last="Gilissen">Christian Gilissen</name><name sortKey="Gilissen, Christian" sort="Gilissen, Christian" uniqKey="Gilissen C" first="Christian" last="Gilissen">Christian Gilissen</name><name sortKey="Gilissen, Christian" sort="Gilissen, Christian" uniqKey="Gilissen C" first="Christian" last="Gilissen">Christian Gilissen</name><name sortKey="Hennekam, Raoul C M" sort="Hennekam, Raoul C M" uniqKey="Hennekam R" first="Raoul C M" last="Hennekam">Raoul C M. Hennekam</name><name sortKey="Hoischen, Alexander" sort="Hoischen, Alexander" uniqKey="Hoischen A" first="Alexander" last="Hoischen">Alexander Hoischen</name><name sortKey="Hoischen, Alexander" sort="Hoischen, Alexander" uniqKey="Hoischen A" first="Alexander" last="Hoischen">Alexander Hoischen</name><name sortKey="Hoischen, Alexander" sort="Hoischen, Alexander" uniqKey="Hoischen A" first="Alexander" last="Hoischen">Alexander Hoischen</name><name sortKey="Kamsteeg, Erik Jan" sort="Kamsteeg, Erik Jan" uniqKey="Kamsteeg E" first="Erik-Jan" last="Kamsteeg">Erik-Jan Kamsteeg</name><name sortKey="Kamsteeg, Erik Jan" sort="Kamsteeg, Erik Jan" uniqKey="Kamsteeg E" first="Erik-Jan" last="Kamsteeg">Erik-Jan Kamsteeg</name><name sortKey="Kamsteeg, Erik Jan" sort="Kamsteeg, Erik Jan" uniqKey="Kamsteeg E" first="Erik-Jan" last="Kamsteeg">Erik-Jan Kamsteeg</name><name sortKey="Knoers, Nine Vam" sort="Knoers, Nine Vam" uniqKey="Knoers N" first="Nine Vam" last="Knoers">Nine Vam Knoers</name><name sortKey="Oud, Machteld M" sort="Oud, Machteld M" uniqKey="Oud M" first="Machteld M" last="Oud">Machteld M. Oud</name><name sortKey="Oud, Machteld M" sort="Oud, Machteld M" uniqKey="Oud M" first="Machteld M" last="Oud">Machteld M. Oud</name><name sortKey="Oud, Machteld M" sort="Oud, Machteld M" uniqKey="Oud M" first="Machteld M" last="Oud">Machteld M. Oud</name><name sortKey="Roeleveld, Nel" sort="Roeleveld, Nel" uniqKey="Roeleveld N" first="Nel" last="Roeleveld">Nel Roeleveld</name><name sortKey="Roeleveld, Nel" sort="Roeleveld, Nel" uniqKey="Roeleveld N" first="Nel" last="Roeleveld">Nel Roeleveld</name><name sortKey="Roeleveld, Nel" sort="Roeleveld, Nel" uniqKey="Roeleveld N" first="Nel" last="Roeleveld">Nel Roeleveld</name><name sortKey="Roepman, Ronald" sort="Roepman, Ronald" uniqKey="Roepman R" first="Ronald" last="Roepman">Ronald Roepman</name><name sortKey="Roepman, Ronald" sort="Roepman, Ronald" uniqKey="Roepman R" first="Ronald" last="Roepman">Ronald Roepman</name><name sortKey="Roepman, Ronald" sort="Roepman, Ronald" uniqKey="Roepman R" first="Ronald" last="Roepman">Ronald Roepman</name><name sortKey="Van Maarle, Merel C" sort="Van Maarle, Merel C" uniqKey="Van Maarle M" first="Merel C" last="Van Maarle">Merel C. Van Maarle</name><name sortKey="Veltman, Joris A" sort="Veltman, Joris A" uniqKey="Veltman J" first="Joris A" last="Veltman">Joris A. Veltman</name><name sortKey="Veltman, Joris A" sort="Veltman, Joris A" uniqKey="Veltman J" first="Joris A" last="Veltman">Joris A. Veltman</name><name sortKey="Veltman, Joris A" sort="Veltman, Joris A" uniqKey="Veltman J" first="Joris A" last="Veltman">Joris A. Veltman</name><name sortKey="Verbeek, Nienke E" sort="Verbeek, Nienke E" uniqKey="Verbeek N" first="Nienke E" last="Verbeek">Nienke E. Verbeek</name><name sortKey="Yntema, Jan Bart L" sort="Yntema, Jan Bart L" uniqKey="Yntema J" first="Jan-Bart L" last="Yntema">Jan-Bart L. Yntema</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Lausch, Ekkehart" sort="Lausch, Ekkehart" uniqKey="Lausch E" first="Ekkehart" last="Lausch">Ekkehart Lausch</name></region><name sortKey="Graul Neumann, Luitgard M" sort="Graul Neumann, Luitgard M" uniqKey="Graul Neumann L" first="Luitgard M" last="Graul-Neumann">Luitgard M. Graul-Neumann</name></country><country name="Suisse"><region name="Canton de Vaud"><name sortKey="Superti Furga, Andrea" sort="Superti Furga, Andrea" uniqKey="Superti Furga A" first="Andrea" last="Superti-Furga">Andrea Superti-Furga</name></region></country><country name="Pologne"><noRegion><name sortKey="Kutkowska Kazmierczak, Anna" sort="Kutkowska Kazmierczak, Anna" uniqKey="Kutkowska Kazmierczak A" first="Anna" last="Kutkowska-Kazmierczak">Anna Kutkowska-Kazmierczak</name></noRegion></country><country name="Turquie"><noRegion><name sortKey="Elcio Lu, Nursel" sort="Elcio Lu, Nursel" uniqKey="Elcio Lu N" first="Nursel" last="Elçio Lu">Nursel Elçio Lu</name></noRegion><name sortKey="Kayserili, Hulya" sort="Kayserili, Hulya" uniqKey="Kayserili H" first="Hulya" last="Kayserili">Hulya Kayserili</name></country><country name="Belgique"><noRegion><name sortKey="Devriendt, Koenraad" sort="Devriendt, Koenraad" uniqKey="Devriendt K" first="Koenraad" last="Devriendt">Koenraad Devriendt</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Belgique/explor/OpenAccessBelV2/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000397 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000397 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Belgique
|area= OpenAccessBelV2
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:EFE630C08BA484FCC659095E33A3C3349589E1E3
|texte= Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement
}}
| This area was generated with Dilib version V0.6.25. |  |