Novel Val606Met mutation in beta myosin heavy chain gene in Chinese pedigrees with familiar hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To screen the disease-causing gene mutation in Chinese patients with familiar hypertrophic cardiomyopathy (HCM) and to analyse the correlation between the genotype and phenotype.</p><p><b>METHODS</b>Eight Chinese pedigrees with HCM and 80 age-matched normal control subjects were studied. The exons in the functional regions of the beta myosin heavy chain gene (beta-MHC) were amplified with PCR and the products were sequenced. The relation between the genotype and phenotype was analyzed.</p><p><b>RESULT</b>Val606Met mutation was identified in exon 16 in one family and Val606Met mutation was identified in 4 out of 8 family members in this pedigree and 3 out of 4 Val606Met carriers suffered from HCM. No similar mutation was identified in controls.</p><p><b>CONCLUSION</b>The Val606Met mutation located at the actin-binding region of the cardiac beta-MHC gene is involved in the pathogenesis of HCM in this Chinese pedigree.</p>

Mutation of Arg723Gly in beta-myosin heavy chain gene in five Chinese families with hypertrophic cardiomyopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypertrophic cardiomyopathy (HCM) is a form of cardiomyopathy with an autosomal dominant inherited disease, which is caused by mutations in at least one of the sarcomeric protein genes. Mutations in the beta-myosin heavy chain (beta-MHC) are the most common cause of HCM. This study was to reveal the disease-causing gene mutations in Chinese population with HCM, and to analyze the correlation between the genotype and phenotype.</p><p><b>METHODS</b>The exons 3 to 26 of MYH7 were amplified by PCR, and the PCR products were sequenced in five non-kin HCM patients. A 17-year-old patient was detected to be an Arg723Gly mutation carrier. Then his family was gene-screened, and the correlation between genotype and phenotype was analyzed.</p><p><b>RESULTS</b>The mutation of Arg723Gly in a Chinese family with HCM was detected for the first time. With a C-G transversion in nucleotide 13,619 of the MYH7 gene, located at the essential light chain interacting region in S1, the replacement of arginine by glycine took place at amino acid residue 723. A two-dimensional echocardiogram showed moderate asymmetrical septal hypertrophy with left atria enlargement. There was no obstruction in the left ventricular outflow tract. In his family, a total of 13 individuals were diagnosed HCM and 5 of them were dead of congestive heart failure at a mean age of 66-year-old. Eight living members were all detected to carry the mutation, in which 3 developed progressive heart failure. Moreover, the heart function of the people evidently deteriorates when their age are older than 50. The mutation and the disease show co-separated.</p><p><b>CONCLUSION</b>The Arg723Gly mutation is a malignant type. In Chinese the mutation has the similar characters to the former report but has low degree malignant.</p>

Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta-myosin heavy chain gene in a Chinese pedigree / 中华心血管病杂志

<p><b>OBJECTIVE</b>Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease and an Arg723Gly mutation in beta-myosin heavy chain (beta-MHC) gene was found in 3 Spanish families with malignant HCM. We detected this gene mutation in 5 Chinese pedigrees with hypertensive cardiomyopathy.</p><p><b>METHODS</b>Five Chinese pedigrees with HCM and 80 age-matched normal control subjects were chosen for the study. The exons in the functional regions of the beta-MHC gene were amplified with PCR and the products were sequenced, genotype and phenotype analyzed.</p><p><b>RESULTS</b>Arg723Gly mutation was identified in exon 20 in one pedigree. In this pedigree, 13 out of 25 family members were diagnosed as HCM, 5 died of heart failure, all HCM patients in this pedigree had Arg723Gly mutation and 3 of them had NYHA III and 2 of them were diagnosed as HCM before the age of 20.</p><p><b>CONCLUSIONS</b>Arg723Gly mutation was also one of the main disease-causing genes in Chinese familial HCM. The mutation of Arg723Gly is a malignant phenotype as shown by early progressive heart failure development and poor prognosis in this pedigree with Arg723Gly mutation.</p>