Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes

Jennifer S. Beighley, Caitlin M. Hudac, Anne B. Arnett, Jessica L. Peterson, Jennifer Gerdts, Arianne S. Wallace, Heather C. Mefford, Kendra Hoekzema, Tychele N. Turner, Brian J. O'Roak, Evan E. Eichler, Raphael A. Bernier

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Background: Variants disruptive to CHD8 (which codes for the protein CHD8 [chromodomain-helicase-DNA-binding protein 8]) are among the most common mutations revealed by exome sequencing in autism spectrum disorder (ASD). Recent work has indicated that CHD8 plays a role in the regulation of other ASD-risk genes. However, it is unclear whether a possible shared genetic ontology extends to the phenotype. Methods: This study (N = 143; 42.7% female participants) investigated clinical and behavioral features of individuals ascertained for the presence of a known disruptive ASD-risk mutation that is 1) CHD8 (CHD8 group) (n = 15), 2) a gene targeted by CHD8 (target group) (n = 22), or 3) a gene without confirmed evidence of being targeted by CHD8 (other gene group) (n = 106). Results: Results indicated shared features between the CHD8 and target groups that included less severe adaptive deficits in communication skills, similar functional language, more social motivation challenges in those with ASD, larger head circumference, higher weight, and lower seizure prevalence relative to the other gene group. Conclusions: These similarities suggest broader genetic ontology accounts for aspects of phenotypic heterogeneity. Improved understanding of the relationships between related disruptive gene events may lead us to improved understanding of shared mechanisms and lead to more focused treatments for individuals with known genetic mutations.

Original languageEnglish
Pages (from-to)123-131
Number of pages9
JournalBiological Psychiatry
Issue number2
StatePublished - Jan 15 2020


  • Autism spectrum disorder
  • CHD8
  • Gene regulation
  • Genetic subtypes
  • Neurodevelopmental disorder
  • Precision medicine


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