Comprehensive genetic screening of 5 sarcomere genes in 93 Japanese patients with hypertrophic cardiomyopathy identified mutations in 28 patients, including the first report of double mutations in 2 probands.
Observational (n=93)
No
What is the prevalence and clinical significance of multiple sarcomere gene mutations in Japanese patients with hypertrophic cardiomyopathy?
Double mutations in sarcomere genes occur in Japanese HCM patients and may be associated with a more severe phenotype, such as earlier onset and greater wall thickness.
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal-dominant pattern of inheritance mainly caused by single heterozygous mutations in sarcomere genes. Although multiple gene mutations have recently been reported in Western countries, clinical implications of multiple mutations in Japanese subjects are not clear. METHODS AND RESULTS: A comprehensive genetic analysis of 5 sarcomere genes (cardiac β-myosin heavy chain gene MYH7, cardiac myosin-binding protein C gene MYBPC3, cardiac troponin T gene TNNT2, α-tropomyosin gene TPM1 and cardiac troponin I gene TNNI3) was performed in 93 unrelated patients and 14 mutations were identified in 28 patients. Twenty-six patients had single heterozygosity (20 in MYBPC3, 4 in MYH7, 1 in TNNT2, 1 in TNNI3), whereas 2 proband patients with familial HCM had double heterozygosity: 1 with P106fs in MYBPC3 and R869C in MYH7 and 1 with R945fs in MYBPC3 and E1049D in MYH7. From the results of the family survey and the previous literature on HCM mutations, P106fs, R945fs and R869C seemed to be pathological mutations and E1049D might be a rare polymorphism. The proband patient with P106fs and R869C double mutation was diagnosed as having HCM at an earlier age (28 years of age) than her relatives with single mutation, and had greater wall thickness with left ventricular outflow obstruction. CONCLUSIONS: One double mutation was identified in a Japanese cohort of HCM patients. Further studies are needed to clarify the clinical significance of multiple mutations including phenotypic severity.
Kubo et al. (Sat,) conducted a observational in Hypertrophic cardiomyopathy (n=93). Genetic screening of 5 sarcomere genes was evaluated on Identification of sarcomere gene mutations. Comprehensive genetic screening of 5 sarcomere genes in 93 Japanese patients with hypertrophic cardiomyopathy identified mutations in 28 patients, including the first report of double mutations in 2 probands.