| Literature DB >> 26785492 |
Jason Homsy1, Samir Zaidi2, Yufeng Shen3, James S Ware4, Kaitlin E Samocha5, Konrad J Karczewski5, Steven R DePalma6, David McKean7, Hiroko Wakimoto7, Josh Gorham7, Sheng Chih Jin2, John Deanfield8, Alessandro Giardini8, George A Porter9, Richard Kim10, Kaya Bilguvar11, Francesc López-Giráldez12, Irina Tikhonova12, Shrikant Mane12, Angela Romano-Adesman13, Hongjian Qi14, Badri Vardarajan15, Lijiang Ma16, Mark Daly5, Amy E Roberts17, Mark W Russell18, Seema Mital19, Jane W Newburger20, J William Gaynor21, Roger E Breitbart20, Ivan Iossifov22, Michael Ronemus22, Stephan J Sanders23, Jonathan R Kaltman24, Jonathan G Seidman7, Martina Brueckner25, Bruce D Gelb26, Elizabeth Goldmuntz27, Richard P Lifton28, Christine E Seidman29, Wendy K Chung30.
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, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients.Entities:
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Year: 2015 PMID： 26785492 PMCID： PMC4890146 DOI： 10.1126/science.aac9396
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728