title: Do mitochondria contribute to left ventricular non-compaction cardiomyopathy? New findings from myocardium of patients with left ventricular non-compaction cardiomyopathy.
abstract: BACKGROUND
  Left ventricular non-compaction cardiomyopathy (LVNC) is a rare congenital cardiomyopathy that is associated with mutations in mitochondrial DNA (mtDNA), however, no study of myocardium mtDNA of LVNC patients has been reported. To identify novel candidate mtDNA variants that may be responsible for the pathogenesis of LVNC, myocardial specimens were examined to investigate pathogenic mtDNA variants.
  
  
  METHODS
  Samples from six patients who were diagnosed with LVNC and underwent heart transplantation were analyzed. The sequence and copy number of mtDNA from these samples were determined by Sanger sequencing and fluorescence-based quantitative polymerase chain reaction, respectively.
  
  
  RESULTS
  Myocardial mtDNA sequences analysis revealed 227 substitution variants, including 157 coding variants and 70 non-coding variants. An m.9856T>C (Ile217Thr) mutation in MT-CO3 from one LVNC patient was found to be a non-haplogroup associated variant, and was rare in the mtDB Human Mitochondrial Genome Database, suggesting that the variant may be pathogenic. And there was statistically significant difference in mtDNA copy number between LVNC patients and normal control subjects. Electron microscopy (EM) of left ventricular myocardium showed abnormality in mitochondrial morphology and disordered sarcomeric organization.
  
  
  CONCLUSIONS
  The identification of mtDNA sequence variants in myocardial specimens may be helpful for further investigation of the underlying pathogenic implications of myocardial mtDNA mutations in LVNC. However, measurement of mtDNA copy number showed that there was lower mtDNA content in myocardium of LVNC patients than in normal controls (P<0.01). Lower mtDNA copy number and morphological abnormalities of mitochondria suggested mitochondrial dysfunction that may be associated with etiology of LVNC.
authors: State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China.
authors: Shenghua
authors: S
authors: Liu
authors: Yuanyuan
authors: Y
authors: Bai
authors: Jie
authors: J
authors: Huang
authors: Hong
authors: H
authors: Zhao
authors: Xiaoling
authors: X
authors: Zhang
authors: Shengshou
authors: S
authors: Hu
authors: Yingjie
authors: Y
authors: Wei
mesh_terms: D000293:Adolescent; D000328:Adult; D009202:Cardiomyopathies / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D054629:Genome, Mitochondrial; D006330:Heart Defects, Congenital / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial