Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease
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Dosyalar
Tarih
2015
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Cell Press
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Development of the human nervous system involves complex interactions among fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families and homozygous loss-of-function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations.
Açıklama
Anahtar Kelimeler
Intellectual-Disability Syndrome, Chromatin Remodeling Complex, Triple T Complex, Rna Helicases, Pontocerebellar Hypoplasia, Alzheimers-Disease, Snx14 Cause, H-Prune, Protein, Mutations
Kaynak
Neuron
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
88
Sayı
3
