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.
Materials and 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.
Conclusion: 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.
Copyright © 2013 Elsevier Inc. All rights reserved.