The clinical presentation caused by truncating CHD8 variants.
Adolescent
Alleles
Amino Acid Substitution
Child
Child, Preschool
DNA-Binding Proteins
/ genetics
Facies
Female
Genetic Association Studies
/ methods
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Male
Neurodevelopmental Disorders
/ diagnosis
Phenotype
Transcription Factors
/ genetics
CHD8
OGID
autism
macrocephaly
overgrowth
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
21
02
2019
revised:
29
03
2019
accepted:
10
04
2019
pubmed:
20
4
2019
medline:
25
7
2020
entrez:
20
4
2019
Statut:
ppublish
Résumé
Variants in the chromodomain helicase DNA-binding protein 8 (CHD8) have been associated with intellectual disability (ID), autism spectrum disorders (ASDs) and overgrowth and CHD8 is one of the causative genes for OGID (overgrowth and ID). We investigated 25 individuals with CHD8 protein truncating variants (PTVs), including 10 previously unreported patients and found a male to female ratio of 2.7:1 (19:7) and a pattern of common features: macrocephaly (62.5%), tall stature (47%), developmental delay and/or intellectual disability (81%), ASDs (84%), sleep difficulties (50%), gastrointestinal problems (40%), and distinct facial features. Most of the individuals in this cohort had moderate-to-severe ID, some had regression of speech (37%), seizures (27%) and hypotonia (27%) and two individuals were non-ambulant. Our study shows that haploinsufficiency of CHD8 is associated with a distinctive OGID syndrome with pronounced autistic traits and supports a sex-dependent penetrance of CHD8 PTVs in humans.
Substances chimiques
CHD8 protein, human
0
DNA-Binding Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
72-84Subventions
Organisme : Medical Research Council
ID : MC_PC_16018
Pays : United Kingdom
Organisme : Department of Health
ID : HICF-1009-003
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT098051
Pays : United Kingdom
Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.