De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus.

ABSTRACT: Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 × 10^-7), SMARCC1 (p = 8.15 × 10^-10), and PTCH1 (p = 1.06 × 10^-6). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 × 10^-4). Together, these probands account for ∼10% of studied cases. Strikingly, all four genes are required for neural tube development and re

SUBMITTER: Furey CG 

PROVIDER: S-EPMC7839075 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature