Key result
In Chinese patients with hypertrophic cardiomyopathy, MYBPC3 double mutations or premature termination codon mutations were significantly correlated with more severe manifestations requiring invasive therapies compared to missense mutations (p=0.01).
Cross-Sectional (n=114)
No
p-value: p=0.01
Targeted next-generation sequencing identified MYBPC3 mutations in 21.9% of Chinese HCM patients, with truncation mutations like p.Y842X associated with severe phenotypes.
May refine HCM prognostic assessment; extends genotype-phenotype data to Chinese cohorts but leaves open prospective validation.
Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death. Mutations in the MYBPC3 gene represent the cause of HCM in ~35% of patients with HCM. However, genetic testing in clinic setting has been limited due to the cost and relatively time-consuming by Sanger sequencing. Here, we developed a HCM Molecular Diagnostic Kit enabling ultra-low-cost targeted gene resequencing in a large cohort and investigated the mutation spectrum of MYBPC3. In a cohort of 114 patients with HCM, a total of 20 different mutations (8 novel and 12 known mutations) of MYBPC3 were identified from 25 patients (21.9%). We demonstrated that the power of targeted resequencing in a cohort of HCM patients, and found that MYBPC3 is a common HCM-causing gene in Chinese patients. Phenotype-genotype analyses showed that the patients with double mutations (n = 2) or premature termination codon mutations (n = 12) showed more severe manifestations, compared with patients with missense mutations (n = 11). Particularly, we identified a recurrent truncation mutation (p.Y842X) in four unrelated cases (4/25, 16%), who showed severe phenotypes, and suggest that the p.Y842X is a frequent mutation in Chinese HCM patients with severe phenotypes.
No takes yet. Share an insight, caveat, or question.
Liu et al. (2015) conducted a cross-sectional in Hypertrophic Cardiomyopathy (n=114). MYBPC3 double mutations or premature termination codon (PTC) mutations vs. MYBPC3 missense mutations was evaluated on Severe manifestations requiring invasive therapies (p=0.01). In Chinese patients with hypertrophic cardiomyopathy, MYBPC3 double mutations or premature termination codon mutations were significantly correlated with more severe manifestations requiring invasive therapies compared to missense mutations (p=0.01).
Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context: