Mitochondrial <i>tRNALeu/Lys</i> and <i>ATPase 6/8</i> Gene Variations in Spinocerebellar Ataxias

Abstract

Background: The spinocerebellar ataxias (SCA) comprise a heterogeneous group of severe late-onset neurodegenerative diseases that are promoted by the expansion of a tandem-arrayed DNA sequence that modifies the primary structure of the protein. Methods: Genomic DNA of 20 patients affected with SCAs was extracted from peripheral blood and screened for deletions in mitochondrial DNA (mtDNA). Sequencing of tRNA^Leu,tRNA^Lys, cytochrome oxidase II, ATPase 6/8 and NADH dehydrogenase I (NDI) genes belonging to mtDNA from patients with SCAs was also carried out to detect the presence of variations. Results: We identified cytosine-adenine-guanine (CAG) trinucleotide repeat expansions in 20 patients. Seven of these patients had at least one nucleotide change in mtDNA. In such cases, 5 nucleotide variations resulted in amino acid changes with two novel variations T8256G and G9010A. Conclusion: SCA patients showed high levels of mtDNA variations in lymphocytes. It can be proposed that the SCA gene proteins (Ataxins) are involved in the complicated intracellular mechanisms that affect cellular organelles and their components, such as the mitochondrial genome. The instability of CAG repeats in polyglutamine diseases such as SCAs and Huntington’s disease might be a causative factor in mtDNA variation or possible damage.

Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction

“…Considerable decrease in the ETC complex V ATPase 6/8 subunits in ADHD cybrids further provides positive evidences in this direction. ATPase 6/8 mutations are associated with many neurodevelopmental disorders including autism [28], [29], with which ADHD shows overlapping syndromes [30]. The decreased transcript level of ATP6 and ATP8 subunits may lead to the lower activity of complex V in ADHD cybrids as our BN-PAGE data shows.These evidences firmly suggest that mitochondrial dysfunction exists in ADHD.…”

Analysis of mitochondrial DNA variations in a Chinese family with spinocerebellar ataxia

“…28 We noticed that in at least one report in which mtDNA variations were claimed as common in individuals with SCA, 27 the revised Cambridge Reference Sequence was misused as a standard for mutation detection. 27 As we and others have discussed previously, this would result in overestimation of the mutation rate. 14,15 In summary, contrary to the results of some previous studies, we found no relationship between mtDNA variations and occurrence of SCA in a Chinese family.…”

“…Some studies have suggested that mtDNA variations are common in these individuals, 26,27 while others claim that they are rare. 28 We noticed that in at least one report in which mtDNA variations were claimed as common in individuals with SCA, 27 the revised Cambridge Reference Sequence was misused as a standard for mutation detection.…”

Research on Mitochondrial DNA Mutations in Patients with SCA3/MJD

“…The two pairs of primers (Tab. 3) used to amplify and sequence the mtDNA SNVs were previously published(S afaei et al 2009). The first pair is ONP25 and ONP185, used for amplifying MT-TK , MT-ATP8 , MT-ATP6 and a portion of the MT-CO2 gene in the mtDNA (approximately 1078 bp).…”