Hypertrophic cardiomyopathy (HCM), a common genetic heart disorder, is often caused by mutations in sarcomere-related genes. While extensively studied in European populations, its genetic basis in Chinese individuals remains poorly understood.
In a groundbreaking cross-sectional study, researchers from West China Hospital and the University of Birmingham analyzed whole-exome sequencing data from 593 Chinese and 1,232 UK HCM patients, along with controls. They found that Chinese patients carry a significantly higher burden of rare variants (52.8% vs. 13.6% in the UK), yet the proportion of pathogenic or likely pathogenic (P/LP) variants was similar between the two groups.
Notably, two mutations—MYBPC3 c.3624del and TNNT2 c.300C>G—were identified as specific to the Chinese cohort, accounting for 2.9% and 1.5% of cases, respectively. The study also uncovered stronger associations with thin filament and myosin light chain genes in Chinese patients, while MYBPC3 non-truncating variants were more prominent in the UK cohort.
Using the tool genebe, researchers reduced the rate of variants of uncertain significance (VUS) to 46.8%, outperforming other classification tools and improving diagnostic clarity.
These findings underscore the importance of ethnicity-specific genetic databases and refined interpretation frameworks to avoid misclassification and enhance clinical management of HCM across diverse populations.