@article{a03848633014479a91179ffe66fe8c1c,
title = "Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes",
abstract = "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.",
keywords = "Autism spectrum disorder, CHD8, Gene regulation, Genetic subtypes, Neurodevelopmental disorder, Precision medicine",
author = "Beighley, {Jennifer S.} and Hudac, {Caitlin M.} and Arnett, {Anne B.} and Peterson, {Jessica L.} and Jennifer Gerdts and Wallace, {Arianne S.} and Mefford, {Heather C.} and Kendra Hoekzema and Turner, {Tychele N.} and O'Roak, {Brian J.} and Eichler, {Evan E.} and Bernier, {Raphael A.}",
note = "Funding Information: This work was supported by the National Institute of Mental Health Grant Nos. MH100047 (to RAB) and MH101221 (to EEE) and National Institute of Child Health and Human Development Grant No. U54 HD083091 to the University of Washington{\textquoteright}s Center on Human Development and Disability. EEE is an investigator of the Howard Hughes Medical Institute. Funding Information: This work was supported by the National Institute of Mental Health Grant Nos. MH100047 (to RAB) and MH101221 (to EEE) and National Institute of Child Health and Human Development Grant No. U54 HD083091 to the University of Washington's Center on Human Development and Disability. EEE is an investigator of the Howard Hughes Medical Institute. Data were presented previously on two occasions: Data presented at 65th Annual Meeting for the American Academy of Child and Adolescent Psychiatry, October 22?27, 2018, Seattle, WA; and 51st Annual Gatlinburg Conference, April 11?13, 2018, San Diego, CA. We thank the children and families for their participation in this study. EEE is on the Scientific Advisory Board of DNAnexus, Inc. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: {\textcopyright} 2019 Society of Biological Psychiatry",
year = "2020",
month = jan,
day = "15",
doi = "10.1016/j.biopsych.2019.07.020",
language = "English",
volume = "87",
pages = "123--131",
journal = "Biological Psychiatry",
issn = "0006-3223",
number = "2",
}