Background Hypoplastic Coronary Artery Disease (HCAD) is a rare congenital malformation. While linked to genes like NOTCH1, its genetic spectrum is incomplete. No prior association with GDF1 exists. Case presentation A 24-year-old male with exertional chest pain underwent coronary computed tomography angiography (CCTA), which revealed right coronary artery (RCA) hypoplasia (diameter 1. 5 mm) and a superficial myocardial bridge (SMB) of the left ramus artery. Whole-exome sequencing identified a novel heterozygous frameshift mutation in GDF1 (NM₀01492. 4: c. 84₉1del; p. Val31ArgfsTer15), validated by Sanger sequencing. According to ACMG guidelines, the variant was classified as likely pathogenic (PVS1 + PM2). Conclusion This is the first report suggesting a potential association between a GDF1 loss-of-function mutation and HCAD and SMB, expanding the phenotypic spectrum of GDF1-related disorders and providing insights into the genetic etiology of congenital coronary anomalies.
Xiang et al. (2026) studied this question.