Background Left ventricular non-compaction cardiomyopathy (LVNC) is a rare congenital cardiomyopathy that is widely believed to be arrest of cardiac development during embryogenesis. Mitochondria, as critical regulators, play an important role in cardiac myocyte differentiation and cardiac development. MtDNA mutations or deletions have been associated with cardiomyopathies. However, no study of mtDNA from cardiac tissue of LVNC patients has been reported.
Methods and Results To identify novel candidate mtDNA variants that may be responsible for the pathogenesis of LVNC, myocardial specimens were examined to research for pathogenic mtDNA variants. Samples from six patients who were diagnosed with LVNC and underwent heart transplantation were analysed. The sequence and copy number of mtDNA from these samples were determined by Sanger sequencing and fluorescence-based quantitative polymerase chain reaction, respectively. 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-haplogroups 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.
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 LVNC patients had a lower mtDNA content than controls (P = 0.003). Lower mtDNA copy number suggested that mitochondria dysfunction may be associated with aetiology of LVNC.