title: Mitochondrial ND5 12338T>C variant is associated with maternally inherited hypertrophic cardiomyopathy in a Chinese pedigree.
abstract: Hypertrophic cardiomyopathy is a primary disorder characterized by asymmetric thickening of the septum and left ventricular wall, which affects 1 in 500 individuals in the general population. Mutations in mitochondrial DNA have been found to be one of the most important causes of hypertrophic cardiomyopathy. Here we report the clinical, genetic and molecular characterization of a Han Chinese family with a likely maternally transmitted hypertrophic cardiomyopathy. Four (2 men/2 women) of 5 matrilineal relatives in this 3-generation family exhibited the variable severity and age at onset of 44 to 79 years old. Sequence analysis of the entire mitochondrial DNA in this pedigree identified the known homoplasmic ND5 12338T>C variant. This mitochondrial DNA haplogroup belongs to the Eastern Asian F2a. The 12338T>C variant, highly evolutionarily conserved, resulted in the replacement of the translation initiating methionine with a threonine, shortening the ND5 polypeptide by 2 amino acids. The occurrence of ND5 12338T>C variant exclusively in maternal members of this Chinese family suggested that the 12338T>C variant is associated with maternally inherited hypertrophic cardiomyopathy. Our findings will provide theoretical basis for genetic counseling of maternally inherited hypertrophic cardiomyopathy.
authors: The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, PR China.
authors: Zhong
authors: Z
authors: Liu
authors: Yanrui
authors: Y
authors: Song
authors: Shulian
authors: S
authors: Gu
authors: Xiangyu
authors: X
authors: He
authors: Xiaoyu
authors: X
authors: Zhu
authors: Yaoyao
authors: Y
authors: Shen
authors: Bifeng
authors: B
authors: Wu
authors: Wei
authors: W
authors: Wang
authors: Shishi
authors: S
authors: Li
authors: Pingping
authors: P
authors: Jiang
authors: Jianhua
authors: J
authors: Lu
authors: Wendong
authors: W
authors: Huang
authors: Qingfeng
authors: Q
authors: Yan
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology*; D002681:China; D004272:DNA, Mitochondrial / Q000235:genetics; D004452:Echocardiography / Q000379:methods; D042967:Electron Transport Complex I / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C481838:MT-ND5 protein, human; D042967:Electron Transport Complex I