Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/86247
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Type: Journal article
Title: Refining analyses of copy number variation identifies specific genes associated with developmental delay
Author: Coe, B.
Witherspoon, K.
Rosenfeld, J.
van Bon, B.
Vulto-van Silfhout, A.
Bosco, P.
Friend, K.
Baker, C.
Buono, S.
Vissers, L.
Schuurs-Hoeijmakers, J.
Hoischen, A.
Pfundt, R.
Krumm, N.
Carvill, G.
Li, D.
Amaral, D.
Brown, N.
Lockhart, P.
Scheffer, I.
et al.
Citation: Nature Genetics, 2014; 46(10):1063-1071
Publisher: Nature Publishing Group
Issue Date: 2014
ISSN: 1061-4036
1546-1718
Statement of
Responsibility: 
Bradley P Coe ... Eric Haan, Jozef Gécz ...et al.
Abstract: Copy number variants (CNVs) are associated with many neurocognitive disorders; however, these events are typically large, and the underlying causative genes are unclear. We created an expanded CNV morbidity map from 29,085 children with developmental delay in comparison to 19,584 healthy controls, identifying 70 significant CNVs. We resequenced 26 candidate genes in 4,716 additional cases with developmental delay or autism and 2,193 controls. An integrated analysis of CNV and single-nucleotide variant (SNV) data pinpointed 10 genes enriched for putative loss of function. Follow-up of a subset of affected individuals identified new clinical subtypes of pediatric disease and the genes responsible for disease-associated CNVs. These genetic changes include haploinsufficiency of SETBP1 associated with intellectual disability and loss of expressive language and truncations of ZMYND11 in individuals with autism, aggression and complex neuropsychiatric features. This combined CNV and SNV approach facilitates the rapid discovery of new syndromes and genes involved in neuropsychiatric disease despite extensive genetic heterogeneity.
Keywords: Humans; Genetic Predisposition to Disease; Carrier Proteins; Nuclear Proteins; Chromosome Mapping; Sequence Analysis, DNA; Autistic Disorder; Developmental Disabilities; Base Sequence; Polymorphism, Single Nucleotide; Molecular Sequence Data; Child; Female; Male; Comparative Genomic Hybridization; Genetic Association Studies; DNA Copy Number Variations; Haploinsufficiency; Intellectual Disability
Rights: © 2014 Nature America Inc. All rights reserved.
RMID: 0030009010
DOI: 10.1038/ng.3092
Appears in Collections:Paediatrics publications

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