Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders

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dc.contributor.authorCostain, Gregory
dc.contributor.authorWalker, Susan
dc.contributor.authorArgiropoulos, Bob
dc.contributor.authorBaribeau, Danielle A
dc.contributor.authorBassett, Anne S
dc.contributor.authorBoot, Erik
dc.contributor.authorDevriendt, Koen
dc.contributor.authorKellam, Barbara
dc.contributor.authorMarshall, Christian R
dc.contributor.authorPrasad, Aparna
dc.contributor.authorSerrano, Moises A
dc.contributor.authorStavropoulos, D. J
dc.contributor.authorTwede, Hope
dc.contributor.authorVermeesch, Joris R
dc.contributor.authorVorstman, Jacob A S
dc.contributor.authorScherer, Stephen W
dc.date.accessioned2019-02-10T01:03:15Z
dc.date.available2019-02-10T01:03:15Z
dc.date.issued2019-02-07
dc.date.updated2019-02-10T01:03:15Z
dc.description.abstractAbstract 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.
dc.identifier.citationJournal of Neurodevelopmental Disorders. 2019 Feb 07;11(1):3
dc.identifier.doihttps://doi.org/10.1186/s11689-019-9263-3
dc.identifier.urihttp://hdl.handle.net/1880/109893
dc.identifier.urihttps://doi.org/10.11575/PRISM/44518
dc.language.rfc3066en
dc.rights.holderThe Author(s).
dc.titleRare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders
dc.typeJournal Article
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