De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies
| Autor: | Josh Gorham, David M. McKean, Stephen Sanders, Elizabeth Goldmuntz, Francesc López-Giráldez, Angela Romano-Adesman, Kaya Bilguvar, James S. Ware, Jonathan G. Seidman, Mark J. Daly, Amy E. Roberts, Konrad J. Karczewski, J. William Gaynor, Richard P. Lifton, Christine E. Seidman, Mark W. Russell, Hongjian Qi, Steven R. DePalma, Jonathan R. Kaltman, Michael Ronemus, Badri N. Vardarajan, Alessandro Giardini, Ivan Iossifov, Roger E. Breitbart, Jason Homsy, Shrikant Mane, Richard B. Kim, Wendy K. Chung, George A. Porter, Samir Zaidi, Hiroko Wakimoto, Jane W. Newburger, Bruce D. Gelb, Kaitlin E. Samocha, Lijiang Ma, Martina Brueckner, Yufeng Shen, Seema Mital, John E. Deanfield, Sheng Chih Jin, Irina Tikhonova |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Genetics
0303 health sciences Mutation Multidisciplinary Heart disease 030204 cardiovascular system & hematology Biology Bioinformatics medicine.disease_cause medicine.disease 3. Good health 03 medical and health sciences 0302 clinical medicine RNA splicing medicine Transcriptional regulation Chromatin modification cardiovascular diseases Gene De novo mutations Exome sequencing 030304 developmental biology |
| Zdroj: | Science. 350:1262-1266 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.aac9396 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|