Mitochondrial diseases caused by mtDNA mutations: a mini-review.

There are several types of mitochondrial cytopathies, which cause a set of disorders, arise as a result of mitochondria's failure. Mitochondria's functional disruption leads to development of physical, growing and cognitive disabilities and includes multiple organ pathologies, essentially disturbing the nervous and muscular systems. The origins of mitochondrial cytopathies are mutations in genes of nuclear DNA encoding mitochondrial proteins or in mitochondrial DNA. Nowadays, numerous mtDNA mutations significant to the appearance and progress of pathologies in humans are detected. In this mini-review, we accent on the mitochondrial cytopathies related to mutations of mtDNA. As well known, there are definite set of symptoms of mitochondrial cytopathies distinguishing or similar for different syndromes. The present article contains data about mutations linked with cytopathies that facilitate diagnosis of different syndromes by using genetic analysis methods. In addition, for every individual, more effective therapeutic approach could be developed after wide-range mutant background analysis of mitochondrial genome.

Association of mutations in the mitochondrial genome with the subclinical carotid atherosclerosis in women.

The importance of the study of an association of mitochondrial DNA mutations with asymptomatic atherosclerosis in women is undeniable. In the present study, a series of PCR with primers for mutation region and further amplificate pyrosequencing were carried out to identify point substitutions or microdeletions of the mitochondrial genome. The results obtained were processed using the original method of estimating the level of heteroplasmy. Five mutations in the mitochondrial genome, namely C3256T, G14709A, G12315A, G13513A and G14846A, in which the heteroplasmy level was associated with the degree of preclinical atherosclerosis in women, were identified. The data obtained in the study showed that C3256T, G14709A and G12315A mutations have a positive correlation with atherosclerosis while G13513A and G14846A mutations have a negative correlation with atherosclerotic lesions. Total mutational load of the mitochondrial genome for C3256T, G14709A, G12315A, G13513A and G14846A mutations explains 68% of the variability of thickness of the carotid intima-medial layer, while the complex of traditional risk factors for cardiovascular diseases explains only 8% of the IMT variability. Data on the correlation between heteroplasmy levels of C3256T, G14709A, G12315A, G13513A and G14846A mutations prompt a suggestion that these mutations may be present on the same haplotypes of mitochondrial genome, associated with atherosclerosis.