Disruptive CHD8 mutations define a subtype of autism early in development.


Journal Article

Autism spectrum disorder (ASD) is a heterogeneous disease in which efforts to define subtypes behaviorally have met with limited success. Hypothesizing that genetically based subtype identification may prove more productive, we resequenced the ASD-associated gene CHD8 in 3,730 children with developmental delay or ASD. We identified a total of 15 independent mutations; no truncating events were identified in 8,792 controls, including 2,289 unaffected siblings. In addition to a high likelihood of an ASD diagnosis among patients bearing CHD8 mutations, characteristics enriched in this group included macrocephaly, distinct faces, and gastrointestinal complaints. chd8 disruption in zebrafish recapitulates features of the human phenotype, including increased head size as a result of expansion of the forebrain/midbrain and impairment of gastrointestinal motility due to a reduction in postmitotic enteric neurons. Our findings indicate that CHD8 disruptions define a distinct ASD subtype and reveal unexpected comorbidities between brain development and enteric innervation.

Full Text

Duke Authors

Cited Authors

  • Bernier, R; Golzio, C; Xiong, B; Stessman, HA; Coe, BP; Penn, O; Witherspoon, K; Gerdts, J; Baker, C; Vulto-van Silfhout, AT; Schuurs-Hoeijmakers, JH; Fichera, M; Bosco, P; Buono, S; Alberti, A; Failla, P; Peeters, H; Steyaert, J; Vissers, LELM; Francescatto, L; Mefford, HC; Rosenfeld, JA; Bakken, T; O'Roak, BJ; Pawlus, M; Moon, R; Shendure, J; Amaral, DG; Lein, E; Rankin, J; Romano, C; de Vries, BBA; Katsanis, N; Eichler, EE

Published Date

  • July 17, 2014

Published In

Volume / Issue

  • 158 / 2

Start / End Page

  • 263 - 276

PubMed ID

  • 24998929

Pubmed Central ID

  • 24998929

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2014.06.017


  • eng

Conference Location

  • United States