The Genetic Characteristics Based on Next Generation Sequencing in Patients With Hypertrophic Cardiomyopathy

Objective: This study aimed to explore the genetic epidemiological characteristics in patients with hypertrophic cardiomyopathy (HCM). Methods: We prospectively enrolled 383 unrelated HCM probands who received genetic testing and 3.0 T cardiac MRI examination, including 118 familial HCM and 265 sporadic HCM. The diagnosis of HCM is based on the diagnostic criteria of the American Heart Association and American College of Cardiology guidelines. Patients with familial HCM underwent targeted next generation sequencing including 117 candidate pathogenic genes associated with cardiomyopathies, while sporadic HCM underwent whole-exome sequencing. The genotypic characteristics were analyzed. Results: Among the 383 unrelated Chinese HCM probands, we reported 56 new pathogenic or likely pathogenic gene site mutations, including 3 new rare non-sarcomeric gene mutations and 53 new sarcomeric gene mutations. According to the analysis of genotypic characteristics, it was found that the frequency of rare genes was 3.4%, and the positive rate of sarcomere protein gene detection was 62.4%. Among them, MYH7 and MYBPC3 are the most common pathogenic genes, accounting for 61.9% of sarcomere protein gene mutations. Additionally, in the included HCM population, there was no significant difference in the positive detection rate of sarcomere protein gene between familial HCM and sporadic HCM (66.1% vs 64%, P = 0.7). The proportion of sporadic HCM carrying polygenic mutations was higher than that of familial HCM (11.2% vs. 1.8%, P = 0.003). Conclusion: We reported 56 new gene mutations, which expanded the gene spectrum of HCM. Additionally, the frequency of rare disease genes in the HCM cohort is 3.4%, and the composition ratio of sarcomere protein gene is similar to that of North American or European HCM populations. However, the gene positive rate of sporadic HCM is similar to that of familial HCM, but the composition ratio of genotypes is different.