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

Autor: Beighley JS; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington. Electronic address: beighj@uw.edu., Hudac CM; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington., Arnett AB; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington., Peterson JL; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington., Gerdts J; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington., Wallace AS; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington., Mefford HC; Department of Pediatrics, University of Washington, Seattle, Washington., Hoekzema K; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington., Turner TN; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington., O'Roak BJ; Department of Molecular & Medical Genetics, Oregon Health and Science University, Portland, Oregon., Eichler EE; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington; Howard Hughes Medical Institute, Seattle Children's Autism Center, Seattle, Washington., Bernier RA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington; Center for Child Health, Behavior, and Disabilities, Seattle Children's Autism Center, Seattle, Washington. Electronic address: rab2@u.washington.edu.
Jazyk: angličtina
Zdroj: Biological psychiatry [Biol Psychiatry] 2020 Jan 15; Vol. 87 (2), pp. 123-131. Date of Electronic Publication: 2019 Jul 30.
DOI: 10.1016/j.biopsych.2019.07.020
Abstrakt: 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.
(Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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