De novo mutations in congenital heart disease with neurodevelopmental and other birth defects
| Autor: | Homsy, J, Zaidi, S, Shen, Y, Ware, JS, Samocha, KE, Wakimoto, H, Gorham, J, Chih Jin, S, Deanfield, J, Giardini, A, Porter Jr., GA, Kim, R, Bilguvar, K, Lopez, F, Tikhonova, I, Mane, S, Romano Adesman, A, Qi, H, Vardarajan, B, Ma, L, Daly, M, Roberts, AE, Russell, MW, Mital, S, Newburger, JW, Gaynor, JW, Breitbart, RE, Iossifov, I, Ronemus, M, Sanders, SJ, Kaltman, JR, Seidman, JG, Brueckner, M, Gelb, BD, Goldmuntz, E, Lifton, RP, Seidman, CE, Chung, WK |
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| Přispěvatelé: | Wellcome Trust |
| Rok vydání: | 2015 |
| Předmět: |
Heart Defects
Congenital INTELLECTUAL DISABILITY GENES Transcription Genetic General Science & Technology Neurogenesis RNA Splicing Nervous System Malformations Congenital Abnormalities Humans Exome cardiovascular diseases RNA Messenger AUTISM Child SPECTRUM OUTCOMES Science & Technology Brain RNA-Binding Proteins Prognosis Multidisciplinary Sciences Repressor Proteins Mutation Science & Technology - Other Topics RNA Splicing Factors |
| Popis: | Congenital heart disease (CHD) patients have increased prevalence of extra-cardiac congenital anomalies (CA) and risk of neurodevelopmental disabilities (NDD). Exome sequencing of 1,213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD and CA but only 2% with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, an mRNA splice regulator. Genes mutated in other cohorts ascertained 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 |
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