Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature
Identifieur interne : 000324 ( Istex/Checkpoint ); précédent : 000323; suivant : 000325Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature
Auteurs : Frédérique Béna [Suisse] ; Damien L. Bruno [Australie] ; Mats Eriksson [Suède] ; Conny Van Ravenswaaij-Arts [Pays-Bas] ; Zornitza Stark [Australie] ; Trijnie Dijkhuizen [Pays-Bas] ; Erica Gerkes [Pays-Bas] ; Stefania Gimelli [Suisse] ; Devika Ganesamoorthy [Australie] ; Ann Charlotte Thuresson [Suède] ; Audrey Labalme [France] ; Marianne Till [France] ; Frédéric Bilan [France] ; Laurent Pasquier [France] ; Alain Kitzis [France] ; Christele Dubourgm [France] ; Massimiliano Rossi [France] ; Armand Bottani [Suisse] ; Maryline Gagnebin [Suisse] ; Damien Sanlaville [France] ; Brigitte Gilbert-Dussardier [France] ; Michel Guipponi [Suisse] ; Arie Van Haeringen [Pays-Bas] ; Marjolein Kriek [Pays-Bas] ; Claudia Ruivenkamp [Pays-Bas] ; Stylianos E. Antonarakis [Suisse] ; Britt Marie Anderlid [Suède] ; Howard R. Slater [Australie] ; Jacqueline Schoumans [Suède, Suisse]Source :
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics [ 1552-4841 ] ; 2013-06.
Descripteurs français
- Wicri :
- topic : Génétique.
English descriptors
- KwdEn :
- Abnormality, Additional cnvs, Affymetrix, Agilent, Agilent technologies, Allele, American journal, Approximate breakpoints, Autism, Autism spectrum disorder, Carrier parents, Chromosome, Cnvs, Cohort, Copy number variants, Custom design, Deletion, Developmental delay, Disease cohorts, Dysmorphisms, Epilepsy, Exon, Exonic, Exonic deletion, Exonic deletions, Genet, Genetics, Genomic, Genomic coordinates, Grant sponsor, Gregor, Heterozygous, Heterozygous deletion, Hypotonia, Incomplete penetrance, Intellectual disability, Intragenic, Intragenic duplication, Isoform, Karolinska institutet, Language delay, Medical genetics part, Mental retardation, Metaphase chromosomes, Microarray, Microarray analysis, Mlpa, Mutation, Ndings, Neurexin, Neurodevelopmental, Neurodevelopmental disorders, Nrxn1, Nrxn1 deletion, Nrxn1 deletions, Nrxn1 exonic deletions, Nrxn1 findings, Nrxn1 gene, Nrxn1 transcript, Nrxn1a, Nrxn1b, Nrxn1b isoform, Nrxn3, Parental testing, Paternal, Penetrance, Phenotype, Phenotypic, Phenotypic severity, Point mutations, Present study, Schaaf, Schizophrenia, Secondary cnvs, Variable expressivity, Zweier.
- Teeft :
- Abnormality, Additional cnvs, Affymetrix, Agilent, Agilent technologies, Allele, American journal, Approximate breakpoints, Autism, Autism spectrum disorder, Carrier parents, Chromosome, Cnvs, Cohort, Copy number variants, Custom design, Deletion, Developmental delay, Disease cohorts, Dysmorphisms, Epilepsy, Exon, Exonic, Exonic deletion, Exonic deletions, Genet, Genetics, Genomic, Genomic coordinates, Grant sponsor, Gregor, Heterozygous, Heterozygous deletion, Hypotonia, Incomplete penetrance, Intellectual disability, Intragenic, Intragenic duplication, Isoform, Karolinska institutet, Language delay, Medical genetics part, Mental retardation, Metaphase chromosomes, Microarray, Microarray analysis, Mlpa, Mutation, Ndings, Neurexin, Neurodevelopmental, Neurodevelopmental disorders, Nrxn1, Nrxn1 deletion, Nrxn1 deletions, Nrxn1 exonic deletions, Nrxn1 findings, Nrxn1 gene, Nrxn1 transcript, Nrxn1a, Nrxn1b, Nrxn1b isoform, Nrxn3, Parental testing, Paternal, Penetrance, Phenotype, Phenotypic, Phenotypic severity, Point mutations, Present study, Schaaf, Schizophrenia, Secondary cnvs, Variable expressivity, Zweier.
Abstract
This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1‐deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the β‐isoform of neurexin‐1 and increased head size, as was recently published in four cases with a deletion involving the C‐terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders. © 2013 Wiley Periodicals, Inc.
Url:
DOI: 10.1002/ajmg.b.32148
Affiliations:
- Australie, France, Pays-Bas, Suisse, Suède
- Auvergne-Rhône-Alpes, Canton de Genève, Canton de Vaud, East Middle Sweden, Groningue (province), Hollande-Méridionale, Nouvelle-Aquitaine, Poitou-Charentes, Rhône-Alpes, Région Bretagne, Svealand, Victoria (État)
- Genève, Groningue, Groningue (ville), Lausanne, Leyde, Lyon, Melbourne, Poitiers, Rennes, Stockholm, Uppsala
- Université Claude Bernard Lyon 1, Université d'Uppsala, Université de Genève, Université de Groningue, Université de Melbourne
Links toward previous steps (curation, corpus...)
Links to Exploration step
ISTEX:D1E528C8DAC9E77D84C92231D14863E2808B7869Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature</title><author><name sortKey="Bena, Frederique" sort="Bena, Frederique" uniqKey="Bena F" first="Frédérique" last="Béna">Frédérique Béna</name></author><author><name sortKey="Bruno, Damien L" sort="Bruno, Damien L" uniqKey="Bruno D" first="Damien L." last="Bruno">Damien L. Bruno</name></author><author><name sortKey="Eriksson, Mats" sort="Eriksson, Mats" uniqKey="Eriksson M" first="Mats" last="Eriksson">Mats Eriksson</name></author><author><name sortKey="Van Ravenswaaij Rts, Conny" sort="Van Ravenswaaij Rts, Conny" uniqKey="Van Ravenswaaij Rts C" first="Conny" last="Van Ravenswaaij-Arts">Conny Van Ravenswaaij-Arts</name></author><author><name sortKey="Stark, Zornitza" sort="Stark, Zornitza" uniqKey="Stark Z" first="Zornitza" last="Stark">Zornitza Stark</name></author><author><name sortKey="Dijkhuizen, Trijnie" sort="Dijkhuizen, Trijnie" uniqKey="Dijkhuizen T" first="Trijnie" last="Dijkhuizen">Trijnie Dijkhuizen</name></author><author><name sortKey="Gerkes, Erica" sort="Gerkes, Erica" uniqKey="Gerkes E" first="Erica" last="Gerkes">Erica Gerkes</name></author><author><name sortKey="Gimelli, Stefania" sort="Gimelli, Stefania" uniqKey="Gimelli S" first="Stefania" last="Gimelli">Stefania Gimelli</name></author><author><name sortKey="Ganesamoorthy, Devika" sort="Ganesamoorthy, Devika" uniqKey="Ganesamoorthy D" first="Devika" last="Ganesamoorthy">Devika Ganesamoorthy</name></author><author><name sortKey="Thuresson, Ann Charlotte" sort="Thuresson, Ann Charlotte" uniqKey="Thuresson A" first="Ann Charlotte" last="Thuresson">Ann Charlotte Thuresson</name></author><author><name sortKey="Labalme, Audrey" sort="Labalme, Audrey" uniqKey="Labalme A" first="Audrey" last="Labalme">Audrey Labalme</name></author><author><name sortKey="Till, Marianne" sort="Till, Marianne" uniqKey="Till M" first="Marianne" last="Till">Marianne Till</name></author><author><name sortKey="Bilan, Frederic" sort="Bilan, Frederic" uniqKey="Bilan F" first="Frédéric" last="Bilan">Frédéric Bilan</name></author><author><name sortKey="Pasquier, Laurent" sort="Pasquier, Laurent" uniqKey="Pasquier L" first="Laurent" last="Pasquier">Laurent Pasquier</name></author><author><name sortKey="Kitzis, Alain" sort="Kitzis, Alain" uniqKey="Kitzis A" first="Alain" last="Kitzis">Alain Kitzis</name></author><author><name sortKey="Dubourgm, Christele" sort="Dubourgm, Christele" uniqKey="Dubourgm C" first="Christele" last="Dubourgm">Christele Dubourgm</name></author><author><name sortKey="Rossi, Massimiliano" sort="Rossi, Massimiliano" uniqKey="Rossi M" first="Massimiliano" last="Rossi">Massimiliano Rossi</name></author><author><name sortKey="Bottani, Armand" sort="Bottani, Armand" uniqKey="Bottani A" first="Armand" last="Bottani">Armand Bottani</name></author><author><name sortKey="Gagnebin, Maryline" sort="Gagnebin, Maryline" uniqKey="Gagnebin M" first="Maryline" last="Gagnebin">Maryline Gagnebin</name></author><author><name sortKey="Sanlaville, Damien" sort="Sanlaville, Damien" uniqKey="Sanlaville D" first="Damien" last="Sanlaville">Damien Sanlaville</name></author><author><name sortKey="Gilbert Ussardier, Brigitte" sort="Gilbert Ussardier, Brigitte" uniqKey="Gilbert Ussardier B" first="Brigitte" last="Gilbert-Dussardier">Brigitte Gilbert-Dussardier</name></author><author><name sortKey="Guipponi, Michel" sort="Guipponi, Michel" uniqKey="Guipponi M" first="Michel" last="Guipponi">Michel Guipponi</name></author><author><name sortKey="Van Haeringen, Arie" sort="Van Haeringen, Arie" uniqKey="Van Haeringen A" first="Arie" last="Van Haeringen">Arie Van Haeringen</name></author><author><name sortKey="Kriek, Marjolein" sort="Kriek, Marjolein" uniqKey="Kriek M" first="Marjolein" last="Kriek">Marjolein Kriek</name></author><author><name sortKey="Ruivenkamp, Claudia" sort="Ruivenkamp, Claudia" uniqKey="Ruivenkamp C" first="Claudia" last="Ruivenkamp">Claudia Ruivenkamp</name></author><author><name sortKey="Antonarakis, Stylianos E" sort="Antonarakis, Stylianos E" uniqKey="Antonarakis S" first="Stylianos E." last="Antonarakis">Stylianos E. Antonarakis</name></author><author><name sortKey="Anderlid, Britt Marie" sort="Anderlid, Britt Marie" uniqKey="Anderlid B" first="Britt Marie" last="Anderlid">Britt Marie Anderlid</name></author><author><name sortKey="Slater, Howard R" sort="Slater, Howard R" uniqKey="Slater H" first="Howard R." last="Slater">Howard R. Slater</name></author><author><name sortKey="Schoumans, Jacqueline" sort="Schoumans, Jacqueline" uniqKey="Schoumans J" first="Jacqueline" last="Schoumans">Jacqueline Schoumans</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:D1E528C8DAC9E77D84C92231D14863E2808B7869</idno><date when="2013" year="2013">2013</date><idno type="doi">10.1002/ajmg.b.32148</idno><idno type="url">https://api.istex.fr/document/D1E528C8DAC9E77D84C92231D14863E2808B7869/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002727</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002727</idno><idno type="wicri:Area/Istex/Curation">002727</idno><idno type="wicri:Area/Istex/Checkpoint">000324</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000324</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Molecular and clinical characterization of 25 individuals with exonic deletions of <hi rend="italic">NRXN1</hi> and comprehensive review of the literature<ref type="note" target="#fn1"></ref><ref type="note" target="#fn2"></ref><ref type="note" target="#fn3"></ref></title><author><name sortKey="Bena, Frederique" sort="Bena, Frederique" uniqKey="Bena F" first="Frédérique" last="Béna">Frédérique Béna</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Service of Genetic Medicine, Geneva University Hospital, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author><author><name sortKey="Bruno, Damien L" sort="Bruno, Damien L" uniqKey="Bruno D" first="Damien L." last="Bruno">Damien L. Bruno</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Eriksson, Mats" sort="Eriksson, Mats" uniqKey="Eriksson M" first="Mats" last="Eriksson">Mats Eriksson</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Womeńs and Childreńs Health, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Van Ravenswaaij Rts, Conny" sort="Van Ravenswaaij Rts, Conny" uniqKey="Van Ravenswaaij Rts C" first="Conny" last="Van Ravenswaaij-Arts">Conny Van Ravenswaaij-Arts</name><affiliation wicri:level="4"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Genetics, University of Groningen, University Medical Center Groningen (UMCG), Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Stark, Zornitza" sort="Stark, Zornitza" uniqKey="Stark Z" first="Zornitza" last="Stark">Zornitza Stark</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Dijkhuizen, Trijnie" sort="Dijkhuizen, Trijnie" uniqKey="Dijkhuizen T" first="Trijnie" last="Dijkhuizen">Trijnie Dijkhuizen</name><affiliation wicri:level="4"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Genetics, University of Groningen, University Medical Center Groningen (UMCG), Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Gerkes, Erica" sort="Gerkes, Erica" uniqKey="Gerkes E" first="Erica" last="Gerkes">Erica Gerkes</name><affiliation wicri:level="4"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Genetics, University of Groningen, University Medical Center Groningen (UMCG), Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Gimelli, Stefania" sort="Gimelli, Stefania" uniqKey="Gimelli S" first="Stefania" last="Gimelli">Stefania Gimelli</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Service of Genetic Medicine, Geneva University Hospital, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author><author><name sortKey="Ganesamoorthy, Devika" sort="Ganesamoorthy, Devika" uniqKey="Ganesamoorthy D" first="Devika" last="Ganesamoorthy">Devika Ganesamoorthy</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Thuresson, Ann Charlotte" sort="Thuresson, Ann Charlotte" uniqKey="Thuresson A" first="Ann Charlotte" last="Thuresson">Ann Charlotte Thuresson</name><affiliation wicri:level="4"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Immunology, Genetics and Pathology, The Rudbeck Laboratory, Uppsala University, Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Labalme, Audrey" sort="Labalme, Audrey" uniqKey="Labalme A" first="Audrey" last="Labalme">Audrey Labalme</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Groupement Hospitalier Est, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Till, Marianne" sort="Till, Marianne" uniqKey="Till M" first="Marianne" last="Till">Marianne Till</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Groupement Hospitalier Est, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Bilan, Frederic" sort="Bilan, Frederic" uniqKey="Bilan F" first="Frédéric" last="Bilan">Frédéric Bilan</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique, Centre Hospitalier Universitaire de Poitiers, Poitiers, France;Université de Poitiers, Poitiers</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Poitou-Charentes</region><settlement type="city">Poitiers</settlement></placeName></affiliation></author><author><name sortKey="Pasquier, Laurent" sort="Pasquier, Laurent" uniqKey="Pasquier L" first="Laurent" last="Pasquier">Laurent Pasquier</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale—Hôpital Sud—CHU Rennes, Rennes</wicri:regionArea><placeName><region type="region">Région Bretagne</region><region type="old region">Région Bretagne</region><settlement type="city">Rennes</settlement></placeName></affiliation></author><author><name sortKey="Kitzis, Alain" sort="Kitzis, Alain" uniqKey="Kitzis A" first="Alain" last="Kitzis">Alain Kitzis</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique, Centre Hospitalier Universitaire de Poitiers, Poitiers, France;Université de Poitiers, Poitiers</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Poitou-Charentes</region><settlement type="city">Poitiers</settlement></placeName></affiliation></author><author><name sortKey="Dubourgm, Christele" sort="Dubourgm, Christele" uniqKey="Dubourgm C" first="Christele" last="Dubourgm">Christele Dubourgm</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale—Hôpital Sud—CHU Rennes, Rennes</wicri:regionArea><placeName><region type="region">Région Bretagne</region><region type="old region">Région Bretagne</region><settlement type="city">Rennes</settlement></placeName></affiliation></author><author><name sortKey="Rossi, Massimiliano" sort="Rossi, Massimiliano" uniqKey="Rossi M" first="Massimiliano" last="Rossi">Massimiliano Rossi</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Groupement Hospitalier Est, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Bottani, Armand" sort="Bottani, Armand" uniqKey="Bottani A" first="Armand" last="Bottani">Armand Bottani</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Service of Genetic Medicine, Geneva University Hospital, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author><author><name sortKey="Gagnebin, Maryline" sort="Gagnebin, Maryline" uniqKey="Gagnebin M" first="Maryline" last="Gagnebin">Maryline Gagnebin</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Service of Genetic Medicine, Geneva University Hospital, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author><author><name sortKey="Sanlaville, Damien" sort="Sanlaville, Damien" uniqKey="Sanlaville D" first="Damien" last="Sanlaville">Damien Sanlaville</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Groupement Hospitalier Est, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1028, CNRS UMR5292, Université Claude Bernard Lyon 1, Equipe TIGER, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement><settlement type="city">Lyon</settlement></placeName><orgName type="university">Université Claude Bernard Lyon 1</orgName></affiliation></author><author><name sortKey="Gilbert Ussardier, Brigitte" sort="Gilbert Ussardier, Brigitte" uniqKey="Gilbert Ussardier B" first="Brigitte" last="Gilbert-Dussardier">Brigitte Gilbert-Dussardier</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique, Centre Hospitalier Universitaire de Poitiers, Poitiers, France;Université de Poitiers, Poitiers</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Poitou-Charentes</region><settlement type="city">Poitiers</settlement></placeName></affiliation></author><author><name sortKey="Guipponi, Michel" sort="Guipponi, Michel" uniqKey="Guipponi M" first="Michel" last="Guipponi">Michel Guipponi</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Service of Genetic Medicine, Geneva University Hospital, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author><author><name sortKey="Van Haeringen, Arie" sort="Van Haeringen, Arie" uniqKey="Van Haeringen A" first="Arie" last="Van Haeringen">Arie Van Haeringen</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Kriek, Marjolein" sort="Kriek, Marjolein" uniqKey="Kriek M" first="Marjolein" last="Kriek">Marjolein Kriek</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Ruivenkamp, Claudia" sort="Ruivenkamp, Claudia" uniqKey="Ruivenkamp C" first="Claudia" last="Ruivenkamp">Claudia Ruivenkamp</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Antonarakis, Stylianos E" sort="Antonarakis, Stylianos E" uniqKey="Antonarakis S" first="Stylianos E." last="Antonarakis">Stylianos E. Antonarakis</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Service of Genetic Medicine, Geneva University Hospital, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Genetic Medicine and Development, University of Geneva, Geneva</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author><author><name sortKey="Anderlid, Britt Marie" sort="Anderlid, Britt Marie" uniqKey="Anderlid B" first="Britt Marie" last="Anderlid">Britt Marie Anderlid</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neuropediatrics, Astrid Lindgren Children's Hospital, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular Medicine and Surgery, CMM, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Slater, Howard R" sort="Slater, Howard R" uniqKey="Slater H" first="Howard R." last="Slater">Howard R. Slater</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Schoumans, Jacqueline" sort="Schoumans, Jacqueline" uniqKey="Schoumans J" first="Jacqueline" last="Schoumans">Jacqueline Schoumans</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular Medicine and Surgery, CMM, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Medical Genetics, Lausanne University Hospital, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Suisse</country></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Correspondence address: Department of Medical Genetics, Lausanne University Hospital, 1011 Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title level="j" type="alt">AMERICAN JOURNAL OF MEDICAL GENETICS PART B: NEUROPSYCHIATRIC GENETICS</title><idno type="ISSN">1552-4841</idno><idno type="eISSN">1552-485X</idno><imprint><biblScope unit="vol">162</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="388">388</biblScope><biblScope unit="page" to="403">403</biblScope><biblScope unit="page-count">16</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2013-06">2013-06</date></imprint><idno type="ISSN">1552-4841</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1552-4841</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abnormality</term><term>Additional cnvs</term><term>Affymetrix</term><term>Agilent</term><term>Agilent technologies</term><term>Allele</term><term>American journal</term><term>Approximate breakpoints</term><term>Autism</term><term>Autism spectrum disorder</term><term>Carrier parents</term><term>Chromosome</term><term>Cnvs</term><term>Cohort</term><term>Copy number variants</term><term>Custom design</term><term>Deletion</term><term>Developmental delay</term><term>Disease cohorts</term><term>Dysmorphisms</term><term>Epilepsy</term><term>Exon</term><term>Exonic</term><term>Exonic deletion</term><term>Exonic deletions</term><term>Genet</term><term>Genetics</term><term>Genomic</term><term>Genomic coordinates</term><term>Grant sponsor</term><term>Gregor</term><term>Heterozygous</term><term>Heterozygous deletion</term><term>Hypotonia</term><term>Incomplete penetrance</term><term>Intellectual disability</term><term>Intragenic</term><term>Intragenic duplication</term><term>Isoform</term><term>Karolinska institutet</term><term>Language delay</term><term>Medical genetics part</term><term>Mental retardation</term><term>Metaphase chromosomes</term><term>Microarray</term><term>Microarray analysis</term><term>Mlpa</term><term>Mutation</term><term>Ndings</term><term>Neurexin</term><term>Neurodevelopmental</term><term>Neurodevelopmental disorders</term><term>Nrxn1</term><term>Nrxn1 deletion</term><term>Nrxn1 deletions</term><term>Nrxn1 exonic deletions</term><term>Nrxn1 findings</term><term>Nrxn1 gene</term><term>Nrxn1 transcript</term><term>Nrxn1a</term><term>Nrxn1b</term><term>Nrxn1b isoform</term><term>Nrxn3</term><term>Parental testing</term><term>Paternal</term><term>Penetrance</term><term>Phenotype</term><term>Phenotypic</term><term>Phenotypic severity</term><term>Point mutations</term><term>Present study</term><term>Schaaf</term><term>Schizophrenia</term><term>Secondary cnvs</term><term>Variable expressivity</term><term>Zweier</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Abnormality</term><term>Additional cnvs</term><term>Affymetrix</term><term>Agilent</term><term>Agilent technologies</term><term>Allele</term><term>American journal</term><term>Approximate breakpoints</term><term>Autism</term><term>Autism spectrum disorder</term><term>Carrier parents</term><term>Chromosome</term><term>Cnvs</term><term>Cohort</term><term>Copy number variants</term><term>Custom design</term><term>Deletion</term><term>Developmental delay</term><term>Disease cohorts</term><term>Dysmorphisms</term><term>Epilepsy</term><term>Exon</term><term>Exonic</term><term>Exonic deletion</term><term>Exonic deletions</term><term>Genet</term><term>Genetics</term><term>Genomic</term><term>Genomic coordinates</term><term>Grant sponsor</term><term>Gregor</term><term>Heterozygous</term><term>Heterozygous deletion</term><term>Hypotonia</term><term>Incomplete penetrance</term><term>Intellectual disability</term><term>Intragenic</term><term>Intragenic duplication</term><term>Isoform</term><term>Karolinska institutet</term><term>Language delay</term><term>Medical genetics part</term><term>Mental retardation</term><term>Metaphase chromosomes</term><term>Microarray</term><term>Microarray analysis</term><term>Mlpa</term><term>Mutation</term><term>Ndings</term><term>Neurexin</term><term>Neurodevelopmental</term><term>Neurodevelopmental disorders</term><term>Nrxn1</term><term>Nrxn1 deletion</term><term>Nrxn1 deletions</term><term>Nrxn1 exonic deletions</term><term>Nrxn1 findings</term><term>Nrxn1 gene</term><term>Nrxn1 transcript</term><term>Nrxn1a</term><term>Nrxn1b</term><term>Nrxn1b isoform</term><term>Nrxn3</term><term>Parental testing</term><term>Paternal</term><term>Penetrance</term><term>Phenotype</term><term>Phenotypic</term><term>Phenotypic severity</term><term>Point mutations</term><term>Present study</term><term>Schaaf</term><term>Schizophrenia</term><term>Secondary cnvs</term><term>Variable expressivity</term><term>Zweier</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1‐deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the β‐isoform of neurexin‐1 and increased head size, as was recently published in four cases with a deletion involving the C‐terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders. © 2013 Wiley Periodicals, Inc.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Pays-Bas</li><li>Suisse</li><li>Suède</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Canton de Genève</li><li>Canton de Vaud</li><li>East Middle Sweden</li><li>Groningue (province)</li><li>Hollande-Méridionale</li><li>Nouvelle-Aquitaine</li><li>Poitou-Charentes</li><li>Rhône-Alpes</li><li>Région Bretagne</li><li>Svealand</li><li>Victoria (État)</li></region><settlement><li>Genève</li><li>Groningue</li><li>Groningue (ville)</li><li>Lausanne</li><li>Leyde</li><li>Lyon</li><li>Melbourne</li><li>Poitiers</li><li>Rennes</li><li>Stockholm</li><li>Uppsala</li></settlement><orgName><li>Université Claude Bernard Lyon 1</li><li>Université d'Uppsala</li><li>Université de Genève</li><li>Université de Groningue</li><li>Université de Melbourne</li></orgName></list><tree><country name="Suisse"><noRegion><name sortKey="Bena, Frederique" sort="Bena, Frederique" uniqKey="Bena F" first="Frédérique" last="Béna">Frédérique Béna</name></noRegion><name sortKey="Antonarakis, Stylianos E" sort="Antonarakis, Stylianos E" uniqKey="Antonarakis S" first="Stylianos E." last="Antonarakis">Stylianos E. Antonarakis</name><name sortKey="Antonarakis, Stylianos E" sort="Antonarakis, Stylianos E" uniqKey="Antonarakis S" first="Stylianos E." last="Antonarakis">Stylianos E. Antonarakis</name><name sortKey="Bottani, Armand" sort="Bottani, Armand" uniqKey="Bottani A" first="Armand" last="Bottani">Armand Bottani</name><name sortKey="Gagnebin, Maryline" sort="Gagnebin, Maryline" uniqKey="Gagnebin M" first="Maryline" last="Gagnebin">Maryline Gagnebin</name><name sortKey="Gimelli, Stefania" sort="Gimelli, Stefania" uniqKey="Gimelli S" first="Stefania" last="Gimelli">Stefania Gimelli</name><name sortKey="Guipponi, Michel" sort="Guipponi, Michel" uniqKey="Guipponi M" first="Michel" last="Guipponi">Michel Guipponi</name><name sortKey="Schoumans, Jacqueline" sort="Schoumans, Jacqueline" uniqKey="Schoumans J" first="Jacqueline" last="Schoumans">Jacqueline Schoumans</name><name sortKey="Schoumans, Jacqueline" sort="Schoumans, Jacqueline" uniqKey="Schoumans J" first="Jacqueline" last="Schoumans">Jacqueline Schoumans</name><name sortKey="Schoumans, Jacqueline" sort="Schoumans, Jacqueline" uniqKey="Schoumans J" first="Jacqueline" last="Schoumans">Jacqueline Schoumans</name></country><country name="Australie"><noRegion><name sortKey="Bruno, Damien L" sort="Bruno, Damien L" uniqKey="Bruno D" first="Damien L." last="Bruno">Damien L. Bruno</name></noRegion><name sortKey="Bruno, Damien L" sort="Bruno, Damien L" uniqKey="Bruno D" first="Damien L." last="Bruno">Damien L. Bruno</name><name sortKey="Ganesamoorthy, Devika" sort="Ganesamoorthy, Devika" uniqKey="Ganesamoorthy D" first="Devika" last="Ganesamoorthy">Devika Ganesamoorthy</name><name sortKey="Ganesamoorthy, Devika" sort="Ganesamoorthy, Devika" uniqKey="Ganesamoorthy D" first="Devika" last="Ganesamoorthy">Devika Ganesamoorthy</name><name sortKey="Slater, Howard R" sort="Slater, Howard R" uniqKey="Slater H" first="Howard R." last="Slater">Howard R. Slater</name><name sortKey="Slater, Howard R" sort="Slater, Howard R" uniqKey="Slater H" first="Howard R." last="Slater">Howard R. Slater</name><name sortKey="Stark, Zornitza" sort="Stark, Zornitza" uniqKey="Stark Z" first="Zornitza" last="Stark">Zornitza Stark</name><name sortKey="Stark, Zornitza" sort="Stark, Zornitza" uniqKey="Stark Z" first="Zornitza" last="Stark">Zornitza Stark</name></country><country name="Suède"><region name="Svealand"><name sortKey="Eriksson, Mats" sort="Eriksson, Mats" uniqKey="Eriksson M" first="Mats" last="Eriksson">Mats Eriksson</name></region><name sortKey="Anderlid, Britt Marie" sort="Anderlid, Britt Marie" uniqKey="Anderlid B" first="Britt Marie" last="Anderlid">Britt Marie Anderlid</name><name sortKey="Anderlid, Britt Marie" sort="Anderlid, Britt Marie" uniqKey="Anderlid B" first="Britt Marie" last="Anderlid">Britt Marie Anderlid</name><name sortKey="Schoumans, Jacqueline" sort="Schoumans, Jacqueline" uniqKey="Schoumans J" first="Jacqueline" last="Schoumans">Jacqueline Schoumans</name><name sortKey="Thuresson, Ann Charlotte" sort="Thuresson, Ann Charlotte" uniqKey="Thuresson A" first="Ann Charlotte" last="Thuresson">Ann Charlotte Thuresson</name></country><country name="Pays-Bas"><region name="Groningue (province)"><name sortKey="Van Ravenswaaij Rts, Conny" sort="Van Ravenswaaij Rts, Conny" uniqKey="Van Ravenswaaij Rts C" first="Conny" last="Van Ravenswaaij-Arts">Conny Van Ravenswaaij-Arts</name></region><name sortKey="Dijkhuizen, Trijnie" sort="Dijkhuizen, Trijnie" uniqKey="Dijkhuizen T" first="Trijnie" last="Dijkhuizen">Trijnie Dijkhuizen</name><name sortKey="Gerkes, Erica" sort="Gerkes, Erica" uniqKey="Gerkes E" first="Erica" last="Gerkes">Erica Gerkes</name><name sortKey="Kriek, Marjolein" sort="Kriek, Marjolein" uniqKey="Kriek M" first="Marjolein" last="Kriek">Marjolein Kriek</name><name sortKey="Ruivenkamp, Claudia" sort="Ruivenkamp, Claudia" uniqKey="Ruivenkamp C" first="Claudia" last="Ruivenkamp">Claudia Ruivenkamp</name><name sortKey="Van Haeringen, Arie" sort="Van Haeringen, Arie" uniqKey="Van Haeringen A" first="Arie" last="Van Haeringen">Arie Van Haeringen</name></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Labalme, Audrey" sort="Labalme, Audrey" uniqKey="Labalme A" first="Audrey" last="Labalme">Audrey Labalme</name></region><name sortKey="Bilan, Frederic" sort="Bilan, Frederic" uniqKey="Bilan F" first="Frédéric" last="Bilan">Frédéric Bilan</name><name sortKey="Dubourgm, Christele" sort="Dubourgm, Christele" uniqKey="Dubourgm C" first="Christele" last="Dubourgm">Christele Dubourgm</name><name sortKey="Gilbert Ussardier, Brigitte" sort="Gilbert Ussardier, Brigitte" uniqKey="Gilbert Ussardier B" first="Brigitte" last="Gilbert-Dussardier">Brigitte Gilbert-Dussardier</name><name sortKey="Kitzis, Alain" sort="Kitzis, Alain" uniqKey="Kitzis A" first="Alain" last="Kitzis">Alain Kitzis</name><name sortKey="Pasquier, Laurent" sort="Pasquier, Laurent" uniqKey="Pasquier L" first="Laurent" last="Pasquier">Laurent Pasquier</name><name sortKey="Rossi, Massimiliano" sort="Rossi, Massimiliano" uniqKey="Rossi M" first="Massimiliano" last="Rossi">Massimiliano Rossi</name><name sortKey="Sanlaville, Damien" sort="Sanlaville, Damien" uniqKey="Sanlaville D" first="Damien" last="Sanlaville">Damien Sanlaville</name><name sortKey="Sanlaville, Damien" sort="Sanlaville, Damien" uniqKey="Sanlaville D" first="Damien" last="Sanlaville">Damien Sanlaville</name><name sortKey="Till, Marianne" sort="Till, Marianne" uniqKey="Till M" first="Marianne" last="Till">Marianne Till</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Istex/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000324 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Checkpoint/biblio.hfd -nk 000324 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Istex
|étape= Checkpoint
|type= RBID
|clé= ISTEX:D1E528C8DAC9E77D84C92231D14863E2808B7869
|texte= Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature
}}
| This area was generated with Dilib version V0.6.33. |  |