Double or compound sarcomere mutations in hypertrophic cardiomyopathy: A potential link to sudden death in the absence of conventional risk factors

摘要: Background Risk stratification strategies employing sarcomere gene mutational analysis have proved imprecise in identifying high-risk patients with hypertrophic cardiomyopathy (HCM). Therefore, additional genetic risk markers that reliably determine which are predisposed to sudden death needed. Objective The objective of this study was whether multiple disease-causing mutations can be regarded as for the absence other conventional factors. Methods Databases 3 HCM centers were accessed, and 18 probands 2 genes encoding proteins cardiac identified. Results Severe disease progression or adverse cardiovascular events occurred 7 these (39%), including (ages 31, 37, 57 years) who experienced arrest but also without evidence factors; survived timely defibrillation therapeutic hypothermia 1 died. These carried distinct heterozygous (including a man inherited mutation independently from each his parents HCM)—that is, double MYBPC3 TNNI3 compound mutations—as only predisposing clinical evident potentially explain their unexpected event. Conclusions observations support emerging hypothesis (or compound) detected by testing may confer dosage effect HCM, thereby progression. In families, associated death, even