Homsy, J., Zaidi, S., Shen, Y., Ware, J. S., Samocha, K. E., Karczewski, K. J., DePalma, S. R., McKean, D., Wakimoto, H., Gorham, J., Jin, S. C., Deanfield, J., Giardini, A., Porter G.A, Jr., Kim, R., Bilguvar, K., López-Giráldez, F., Tikhonova, I., Mane, S., Romano-Adesman, A., Qi, H., Vardarajan, B., Ma, L., Daly, M., Roberts, A. E., Russell, M. W., Mital, S., Newburger, J. W., Gaynor, J. W., Breitbart, R. E., Iossifov, I., Ronemus, M., Sanders, S. J., Kaltman, J. R., Seidman, J. G., Brueckner, M., Gelb, B. D., Goldmuntz, E., Lifton, R. P., Seidman, C. E., Chung, W. K. (December 2015) De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science, 350 (6265). pp. 1262-1266. ISSN 00368075
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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 ofmRNA 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.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cardiovascular diseases bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > de novo mutation neurobiology |
| CSHL Authors: | |
| Communities: | CSHL labs > Iossifov lab CSHL labs > Wigler lab |
| Depositing User: | Matt Covey |
| Date: | 4 December 2015 |
| Date Deposited: | 14 Dec 2015 20:41 |
| Last Modified: | 02 Oct 2019 14:58 |
| PMCID: | PMC4890146 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/32173 |
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