Clinical Manifestations of Hypertrophic Cardiomyopathy Patients with Double Mutations in MYBPC3 Gene
Objective To clarify the clinical manifestations of hypertrophic cardiomyopathy(HCM)patients with double MYBPC3 gene mutations.Methods A total of 1 444 unrelated HCM probands were recruited,including 938 cases who underwent whole exome sequencing and 506 cases who underwent panel sequencing of 8 sarcomere genes.The variants located in 8 sarcomere genes detected in patients were classified according to the guidelines of the American Society of Genetics and Genomics.Patients were divided into MYBPC3 double mutation group,other double mutation group,single mutation group,and no mutation group based on the number of the variants.Genotyping of MYBPC3 double mutation patients were performed using T-vector cloning and sequencing.The primary endpoint was cardiovascular death.Results Twelve(0.8%)unrelated HCM patients were identified as carring double MYBPC3 mutations,65(4.5%)carried double mutations in other sarcomere genes,583(40.5%)carried single mutations,and 781(54.2%)had no sarcomere gene mutations.Over a(6.9±4.5)years follow-up period,patients with MYBPC3 double mutations were found to have a higher risk of cardiovascular death compared to other patients(Log rank P=1.19×10-10).Among the MYBPC3 double patients,4 patients were identified as having trans-compound mutations,while the genotype of the remaining 8 patients remained uncertain.No significant difference was observed in the risk of cardiovascular death between patients with trans compound mutations and other MYBPC3 gene double mutations during the follow-up period(Log rank P=0.23).Conclusion HCM patients harboring double mutations in MYBPC3 gene show poor prognosis and should be followed closely.