Jin, Sheng ChihHomsy, JasonZaidi, SamirLu, QiongshiMorton, SarahDePalma, StevenZeng, XueQi, HongjianChang, WeniSierant, Michael C.Hung, Wei-ChienHaider, ShozebZhang, JunhuiKnight, JamesBjornson, Robert D.Castaldi, ChristopherTikhonoa, Irina R.Bilguvar, KayaMane, Shrikant M.Sanders, Stephan J.Mital, SeemaRussell, MarkGaynor, WilliamDeanfield, JohnGiardini, AlessandroPorter, George A.Srivastava, DeepakLo, Cecelia W.Shen, YufengWatkins, W. ScottYandell, MarkYost, H. JosephTristani-Firouzi, MartinNewburger, Jane W.Roberts, Amy E.Kim, RichardZhao, HongyuKaltman, Jonathan R.Goldmuntz, ElizabethChung, Wendy K.Seidman, JonathanGelb, Bruce D.Seidman, ChristineLifton, Richard P.Brueckner, Martina2018-05-302017Jin, 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.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37067917Congenital 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.en-USJournal Article2018-05-3010.1038/ng.3970