Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders.
J Neurodev Disord
; 11(1): 3, 2019 02 07.
Article
em En
| MEDLINE
| ID: mdl-30732576
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Adaptadoras de Transdução de Sinal
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Variações do Número de Cópias de DNA
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Transtornos do Neurodesenvolvimento
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Sequenciamento Completo do Genoma
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Proteínas do Tecido Nervoso
Limite:
Adult
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurodev Disord
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Canadá