Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands
| العنوان: | Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands |
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| المؤلفون: | Cecelia W. Lo, Stephen Sanders, Sarah U. Morton, Irina R. Tikhonoa, Samir Zaidi, Elizabeth Goldmuntz, Hongjian Qi, Richard B. Kim, Jonathan R. Kaltman, Jonathan G. Seidman, Xue Zeng, Jason Homsy, George A. Porter, W. Scott Watkins, Deepak Srivastava, Weni Chang, Martin Tristani-Firouzi, Seema Mital, James R. Knight, Qiongshi Lu, Steven R. DePalma, John E. Deanfield, Christopher Castaldi, J. William Gaynor, Yufeng Shen, Bruce D. Gelb, Mark W. Russell, Richard P. Lifton, Alessandro Giardini, Kaya Bilguvar, Wendy K. Chung, Jane W. Newburger, H. Joseph Yost, Sheng Chih Jin, Mark Yandell, Martina Brueckner, Shrikant Mane, Robert D. Bjornson, Wei Chien Hung, Amy E. Roberts, Junhui Zhang, Christine E. Seidman, Michael C. Sierant, Hongyu Zhao, Shozeb Haider |
| المصدر: | Nature genetics Nature genetics, vol 49, iss 11 |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Heart Defects, Congenital, Risk, Adult, Male, 0301 basic medicine, Proband, Heterozygote, Heart disease, Gene Expression, Genome-wide association study, Biology, Medical and Health Sciences, Article, Growth Differentiation Factor 1, Congenital, 03 medical and health sciences, Genotype, Genetics, medicine, Humans, Genetic Predisposition to Disease, Exome, cardiovascular diseases, Autistic Disorder, Child, Exome sequencing, Heart Defects, Tetralogy of Fallot, Myosin Heavy Chains, Homozygote, Case-control study, High-Throughput Nucleotide Sequencing, Biological Sciences, Vascular Endothelial Growth Factor Receptor-3, medicine.disease, Pedigree, 3. Good health, Editorial, 030104 developmental biology, Case-Control Studies, Mutation, Female, Cardiac Myosins, Genome-Wide Association Study, Developmental Biology |
| الوصف: | Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ∼5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ∼11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ∼3% of isolated CHD patients and ∼28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance, and 12 genes not previously implicated in CHD had >70% probability of being disease related. DNMs in ∼440 genes were inferred to contribute to CHD. Striking overlap between genes with damaging DNMs in probands with CHD and autism was also found. |
| وصف الملف: | application/pdf |
| تدمد: | 1546-1718 1061-4036 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::901990cdfca7f6f14265588f9eac4db8Test https://doi.org/10.1038/ng.3970Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....901990cdfca7f6f14265588f9eac4db8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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