{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:14:40Z","timestamp":1791296080230,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T00:00:00Z","timestamp":1453248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000096","name":"Scottish Rite Charitable Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000096","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:label\/><jats:p>Mutations in chromodomain helicase DNA\u2010binding domain 8 (<jats:italic>CHD8<\/jats:italic>) have been identified in independent genotyping studies of autism spectrum disorder. To better understand the phenotype associated with <jats:italic>CHD8<\/jats:italic> mutations, we genotyped all <jats:italic>CHD8<\/jats:italic> exons in carefully assessed cohorts of autism (n\u2009=\u2009142), schizophrenia (SCZ; n\u2009=\u2009143), and intellectual disability (ID; n\u2009=\u200994). We identified one frameshift mutation, seven non\u2010synonymous variants, and six synonymous variants. The frameshift mutation, p.Asn2092Lysfs*2, which creates a premature stop codon leading to the loss of 212 amino acids of the protein, was from an autism case on whom we present multiple clinical assessments and pharmacological treatments spanning more than 10 years. RNA and protein analysis support a model where the transcript generated from the mutant allele results in haploinsufficiency of <jats:italic>CHD8<\/jats:italic>. This case report supports the association of <jats:italic>CHD8<\/jats:italic> mutations with classical autism, macrocephaly, infantile hypotonia, speech delay, lack of major ID, and psychopathology in late adolescence caused by insufficient dosage of <jats:italic>CHD8<\/jats:italic>. Review of 16 other <jats:italic>CHD8<\/jats:italic> mutation cases suggests that clinical features and their severity vary considerably across individuals; however, these data support a <jats:italic>CHD8<\/jats:italic> mutation syndrome, further highlighting the importance of genomic medicine to guide clinical assessment and treatment. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37566","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T23:18:45Z","timestamp":1453331925000},"page":"1225-1235","source":"Crossref","is-referenced-by-count":44,"title":["A de novo frameshift mutation in chromodomain helicase DNA\u2010binding domain 8 (CHD8): A case report and literature review"],"prefix":"10.1002","volume":"170","author":[{"given":"Nancy","family":"Merner","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery McGill University Montreal Quebec Canada"},{"name":"Department of Human Genetics 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