title: The novel mitochondrial 16S rRNA 2336T>C mutation is associated with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is a primary disorder characterised by asymmetric thickening of septum and left ventricular wall, with a prevalence of 0.2% in the general population.
  
  
  OBJECTIVE
  To describe a novel mitochondrial DNA mutation and its association with the pathogenesis of HCM.
  
  
  RESULTS
  All maternal members of a Chinese family with maternally transmitted HCM exhibited variable severity and age at onset, and were implanted permanent pacemakers due to complete atrioventricular block (AVB). Nuclear gene screening (MYH7, MYBPC3, TNNT2 and TNNI3) was performed, and no potential pathogenic mutation was identified. Mitochondrial DNA sequencing analysis identified a novel homoplasmic 16S rRNA 2336T>C mutation. This mutation was exclusively present in maternal members and absent in non-maternal members. Conservation index by comparison to 16 other vertebrates was 94.1%. This mutation disturbs the 2336U-A2438 base pair in the stem-loop structure of 16S rRNA domain III, which is involved in the assembly of mitochondrial ribosome. Oxygen consumption rate of the lymphoblastoid cells carrying 2336T>C mutation had decreased by 37% compared with controls. A reduction in mitochondrial ATP synthesis and an increase in reactive oxidative species production were also observed. Electron microscopic analysis indicated elongated mitochondria and abnormal mitochondrial cristae shape in mutant cells.
  
  
  CONCLUSIONS
  It is suggested that the 2336T>C mutation is one of pathogenic mutations of HCM. This is the first report of mitochondrial 16S rRNA 2336T>C mutation and an association with maternally inherited HCM combined with AVB. Our findings provide a new insight into the pathogenesis of HCM.
authors.affiliation: The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Song
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Xiangyu
authors.initials: X
authors.lastname: He
authors.forename: Shishi
authors.initials: S
authors.lastname: Li
authors.forename: Bifeng
authors.initials: B
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shulian
authors.initials: S
authors.lastname: Gu
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhu
authors.forename: Xuexiang
authors.initials: X
authors.lastname: Wang
authors.forename: Qiyin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yu
authors.initials: Y
authors.lastname: Dai
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012336:RNA, Ribosomal, 16S / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; D012336:RNA, Ribosomal, 16S