Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands
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Author
Jin, Sheng Chih
Zaidi, Samir
Lu, Qiongshi
Morton, Sarah
Zeng, Xue
Qi, Hongjian
Chang, Weni
Sierant, Michael C.
Hung, Wei-Chien
Haider, Shozeb
Zhang, Junhui
Knight, James
Bjornson, Robert D.
Castaldi, Christopher
Tikhonoa, Irina R.
Bilguvar, Kaya
Mane, Shrikant M.
Sanders, Stephan J.
Mital, Seema
Russell, Mark
Gaynor, William
Deanfield, John
Giardini, Alessandro
Porter, George A.
Srivastava, Deepak
Lo, Cecelia W.
Shen, Yufeng
Watkins, W. Scott
Yandell, Mark
Yost, H. Joseph
Tristani-Firouzi, Martin
Newburger, Jane W.
Roberts, Amy E.
Kim, Richard
Zhao, Hongyu
Kaltman, Jonathan R.
Goldmuntz, Elizabeth
Chung, Wendy K.
Gelb, Bruce D.
Lifton, Richard P.
Brueckner, Martina
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ng.3970Metadata
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Jin, S. C., J. Homsy, S. Zaidi, Q. Lu, S. Morton, S. R. DePalma, X. Zeng, et al. 2017. “Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.” Nature genetics 49 (11): 1593-1601. doi:10.1038/ng.3970. http://dx.doi.org/10.1038/ng.3970.Abstract
Congenital heart disease (CHD) is the leading cause of mortality from birth defects. 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 are inferred to contribute to CHD. There was striking overlap between genes with damaging DNMs in probands with CHD and autism.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675000/pdf/Terms of Use
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