huntington’s disease and mitochondrial dna deletions: an incident or a regular mechanism for mutant huntingtin protein and cag repeats expansion?!

the mitochondrial dna (mtdna) may play an essential role in the pathogenesis of the respiratory chain complex activities in neurodegenerative disorders such as huntington’s disease (hd). research studies have been conducted to determine the possible levels of mitochondrial defect (deletion) in hd patients and the interaction between the expanded huntingtin gene as a nuclear gene and mitochondria as a cytoplasmic organelle. to determine mtdna damage, we investigated deletions based in four areas of mitochondrial dna, in a group of 60 iranian patients clinically diagnosed with hd and 70 healthy controls. a total of 41 patients out of 60 had cag expansion (group a). about 19 patients did not show expansion but had clinical symptoms of hd (group b). mtdna deletions were classified into four groups according to size 9 kb, 7.5 kb, 7 kb, and 5 kb. we found one of the four mtdna deletions in at least 90% of samples. multiple deletions were also observed in 63% of hd patients. none of the normal controls (group c) showed mtdna deletions. the sizes or locations of the deletions did not show a clear correlation with expanded cag repeats and age in our samples. the study presented evidence that hd patients had higher frequencies of mtdna deletions in lymphocytes in comparison to the controls. it is thus proposed that cag repeats instability and mutant htt are causative factors in mtdna damage.