Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders / G. COSTAIN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p. Titre : Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders Type de document : texte imprimé Auteurs : G. COSTAIN, Auteur ; S. WALKER, Auteur ; B. ARGIROPOULOS, Auteur ; D. A. BARIBEAU, Auteur ; A. S. BASSETT, Auteur ; E. BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; B. KELLAM, Auteur ; C. R. MARSHALL, Auteur ; A. PRASAD, Auteur ; M. A. SERRANO, Auteur ; D. J. STAVROPOULOS, Auteur ; H. TWEDE, Auteur ; J. R. VERMEESCH, Auteur ; J. A. S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur Article en page(s) : 3 p. Langues : Anglais (eng) Mots-clés : Adhd  Autism  Copy number variation  Dmxl2  Grik5  Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders [texte imprimé] / G. COSTAIN, Auteur ; S. WALKER, Auteur ; B. ARGIROPOULOS, Auteur ; D. A. BARIBEAU, Auteur ; A. S. BASSETT, Auteur ; E. BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; B. KELLAM, Auteur ; C. R. MARSHALL, Auteur ; A. PRASAD, Auteur ; M. A. SERRANO, Auteur ; D. J. STAVROPOULOS, Auteur ; H. TWEDE, Auteur ; J. R. VERMEESCH, Auteur ; J. A. S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur . - 3 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p. Mots-clés : Adhd  Autism  Copy number variation  Dmxl2  Grik5  Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

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