De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies
Harvard University · Massachusetts General Hospital · +25 more institutions
Abstract
Congenital heart disease (CHD) patients have an increased prevalence of extracardiac congenital anomalies (CAs) and risk of neurodevelopmental disabilities (NDDs). Exome sequencing of 1213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in the developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD, and CA but only 2% of patients with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, a regulator of mRNA splicing. Genes mutated in other cohorts examined for NDD were enriched in CHD cases,…
Citation impact
- FWCI
- 45.14
- Percentile
- 100%
- References
- 28
Authors
41- JHJason HomsyCorresponding
Harvard University, Massachusetts General Hospital
- SZSamir ZaidiCorresponding
Yale University
- YSYufeng ShenCorresponding
Columbia University Irving Medical Center
- JSJames S. WareCorresponding
Harvard University, Royal Brompton & Harefield NHS Foundation Trust, Imperial College London
- KEKaitlin E. Samocha
Harvard University, Massachusetts General Hospital
Topics & keywords
- Heart disease
- Exome sequencing
- Medicine
- Neurodevelopmental disorder
- Pediatrics
- Disease
- Genotyping
- Exome
Funding
- HHHoward Hughes Medical Institute
- SFSimons Foundation
- WWellcome
- HMHarvard Medical School
- HAHeart and Stroke Foundation of Canada
- BHBritish Heart Foundation
- ARArthritis Research UK
- AOAcademy of Medical Sciences
- ICImperial College London
- FLFondation Leducq
- MRMedical Research CouncilAward: MR/K006584/1
- NHNational Heart, Lung, and Blood Institute