Multifaceted analysis of noncoding and coding de novo variants implicates NOTCH signaling pathway in tetralogy of Fallot in Chinese population.

ABSTRACT: Tetralogy of Fallot (TOF) is the most common cyanotic heart defect in neonates. While there is compelling evidence of genetic contribution to the etiology of TOF, the contribution of noncoding variants to the development of the defect remains unexplored. Potentially damaging noncoding de novo variants (NC DNVs) were detected from 141 Chinese nonsyndromic TOF trios (CHN-TOF) and compared with those detected in the Pediatric Cardiac Genomics Consortium (PCGC). Bioinformatic analyses on noncoding and previously detected coding DNVs were performed to identify developmental pathways affected in TOF. Chinese but not PCGC-TOF patients showed a notably increased burden of putative damaging NC DNVs (n = 249). In Chinese, NC and coding DNVs were predominantly associated with cardiomyocyte differenti

SUBMITTER: Lin Q 

PROVIDER: S-EPMC11910093 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature