Integrative Genomics Implicates Genetic Disruption of Prenatal Neurogenesis in Congenital Hydrocephalus

摘要: METHODSExome analysis of 381 radiographically-confirmed, neurosurgically-treated sporadic CH probands (including 232 case-parent trios) identified genes with rare de novo or transmitted mutations conferring disease risk. Transcriptome analyses identified mid-gestational brain modules and cell-types enriched for cohort-determined CH risk genes, known genes previously implicated in isolated and syndromic forms of CH, and risk genes of Autism Spectrum Disorder (ASD) and Developmental Disorder (DD).RESULTSExome analysis reveals 9 high confidence genes and 55 probable risk genes harboring CH-linked mutations. Together, cohort-determined and known CH genes enrich in a single network (“yellow” module) associated with ASD and DD. Functional profiling of the yellow module yields terms of cell and neuronal differentiation, congenital anomalies of craniofacial development, and behavioral …