The clinical presentation caused by truncating CHD8 variants.

Authors:
Sofia Douzgou
Sofia Douzgou
Institute of Child Health
Greece
Hui Wen Liang
Hui Wen Liang
School of Biological Sciences
Kay Metcalfe
Kay Metcalfe
St Mary's Hospital
United Kingdom
Suresh Somarathi
Suresh Somarathi
Manchester Centre for Genomic Medicine
Marc Tischkowitz
Marc Tischkowitz
McGill University
Montréal | Canada
Usha Kini
Usha Kini
St. John's Medical College and Hospital
India
Shane McKee
Shane McKee
Belfast City Hospital
United Kingdom

Clin Genet 2019 Apr 18. Epub 2019 Apr 18.

Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK.

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.

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Source
http://doi.wiley.com/10.1111/cge.13554
Publisher Site
http://dx.doi.org/10.1111/cge.13554DOI Listing
April 2019
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