Mutation of Arg723Gly in β-myosin heavy chain gene in five Chinese families with hypertrophic cardiomyopathy

( views:99, downloads:0 )
YANG Jun-hua()
ZHAO Cai-ming()
JIANG Wen-ping()
ZHENG Dong-dong()
DONG Ning-zheng()
YANG Xiang-jun()
SONG Jian-ping()
JIANG Ting-bo()
CHENG Xu-jie()
LI Hong-xia()
ZHOU Bing-yuan()
Journal Title:
Volume 119, Issue 21, 2006
Key Word:
cardiomyopathy, hypertrophic, familial;myosin heavy chain;mutation;genotype;phenotype

Abstract: Background 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 (β-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.Methods 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.Results 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.Conclusion The Arg723Gly mutation is a malignant type. In Chinese the mutation has the similar characters to the former report but has low degree malignant.

  • [1]Maron B J,Gardin JM,Flack JM,Gidding SS,Kurosaki TT,Bild DE.Prevalence of hypertrophic cardiomyopathy in a general population of young adults:echocardiographic analysis of 4111 subjects in the CADIA study:coronary artery risk development in (young) adults.Circulation 1995; 92:785-789.
  • [2]Zou Y,Song L,Wang Z,Ma A,Liu T,Gu H,et al.Prevalence of idiopathic hypertrophic cardiomyopathy in China:a population-based echocardiographicanalysis of 8080 adults.Am J Med 2004; 116:14-18.
  • [3]Ho HH,Lee KL,Lau CP,Tse HF.Clinical characteristics of and long-term outcome in Chinese patients with hypertrophic cardiomyopathy.Am J Med 2004; 116:19-23.
  • [4]Wang P,Zou Y,Fu Z,Zhou X,Hui R.MYBPC3 polymorphism is a modifier for expression of cardiac hypertrophy in patients with hypertrophic cardiomyopathy.Biochem Biophys Res Commun 2005; 329:796-799.
  • [5]Marian AJ,Roberts R.Recent advances in the molecular genetics of hypertrophic cardiomyopathy.Circulation 1995; 92:1336-1347.
  • [6]Seidman CE,Seidman JG.Molecular genetic studies of familial hypertrophic cardiomyopathy.Basic Res Cardiol 1998; 93 Suppl 3:13-16.
  • [7]Song L,Zou Y,Wang J,Wang Z,Zhen Y,Lou K,et al.Mutations profile in Chinese patients with hypertrophic cardiomyopathy.Clinica Chimica Acta 2005; 351:209-216.
  • [8]Jaenicke T,Diederich KW,Haas W,Schleich J,Lichter P,Pfordt M,et al.The complete sequence of the human beta-myosin heavy chain gene and an analysis of its product.Genomics 1990; 8:194-206.
  • [9]Liew CC,Sole M J,Yamauchi-Takihara K,Kellam B,Anderson DH,Lin LP,et al.Complete sequence and organization of the human cardiac beta-myosin heavy chain gene.Nucleic Acids Res 1990; 18:3647-3651.
  • [10]Watkins H.Hypertrophic cardiomyopathy:from molecular and genetic mechanisms to clinical management.Eur Heart J Suppl 2001; 3 Suppl L:L43-L50.
  • [11]Schwarts K,Carrier L,Guicheney P,Komajda M.Molecular basis of familial cardiomyopathies.Circulation 1995; 91:532-540.
  • [12]Thierfelder L,Watkins H,MacRae C,Lamas R,McKenna W,Vosberg HP,et al.Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy:a disease of the sarcomere.Cell 1994;77:701-712.
  • [13]Rayment I,Holden HM,Whittaker M,Yohn CB,Lorenz M,Holmes KC,et al.Structure of the actin-myosin complex and its implications for muscle contraction.Science 1993;261:58-65.
  • [14]Lowey S.Functional consequences of mutations in the myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy.Trends Cardiovasc Med 2002; 12:348-354.
  • [15]Enjuto M,Francino A,Navarro-Lopez F,Viles D,Pare JC,Ballesta AM.Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in β-myosin heavy chain gene.J Mol Cell Cardiol2000; 32:2307-2313.
  • [16]Zou YB,Wang JZ,Wu PX,Zheng WY,Lu SL,Hui RT,et al.Ala26Val mutation in beta-myosin heavy chain gene:a hot spot mutation in Chinese hypertrophic cardiomyopathy.Chin J Cardiol (Chin) 2002; 30:473-476.
  • [17]Song L,Xu R,Wu GR,Wang JZ,Zheng WY,Zou YB,et al.The genotype-phynotype correlation of the betamyosin heavy chain gene Arg663Cys and Arg663His mutation in familial hypertrophic cardiomyopathy.Chin J Cardiol (Chin) 2002; 30:131-135.
  • [18]Song L,Huang XH,Hui RT,Gao JH,Zheng WY,Teng SY,et al.Mutations in the gene encoding for cardiac beta-myosin heavy chain in Chinese families with hypertrophic cardiomyopathy.Chin J Cardiol (Chin) 2001;29:348-352.
  • [19]Kuang SQ,Yu JD,Lu L,He RM,Gong LS,Chen SJ,et al.Missense mutation in the cardiac β-myosin heavy chain gene in patient with hypertrophic cadiomyopathy.Chin J Cardiol (Chin) 1996; 24:111-114.
  • [20]Xie WL,Liu WL,Hu DY,Cui W,Zhu TG,Fan DY,et al.Mutations in beta myosin heavy chain gene:one mutation Ile736Thr identified firstly in Chinese with hypertrophic cardiomyopathy and the correlation between their genotype and phynotype.Chin J Cardiol (Chin) 2004; 12:1087-1089.
  • [21]Huang XH,Song L,Ma AQ,Gao JH,Zheng WY,Zhou XL,et al.A malignant phenotype of hypertrophic cardiomyopathy caused by Arg719GIn cardiac beta-myosin heavy-chain mutation in a Chinese family.Clinica Chimica Acta 2001; 310:131-139.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615