Mitochondrial DNA damage in spinal and bulbar muscular atrophy patients and carriers

Abstract Background Mitochondrial DNA (mtDNA) damage may be involved in the pathogenesis of spinal and bulbar muscular atrophy (SBMA). Methods We recruited 20 SBMA patients, 20 SBMA female carriers, and 20 normal age-matched subjects. Mitochondrial DNA damage in the 3 groups of subjects was evaluated using three novel mtDNA oxidative markers: mtDNA copy number, 4977 bp deletion of mtDNA (mtDNA 4977 ) and oxidative modification of mtDNA index (mtDNA ∆CT ) in leukocytes. Results Decreased leukocyte mtDNA copy number, increased mtDNA ∆CT value, and increased frequency of mtDNA 4977 which correspond to the number of CAG repeats in the mutated androgen receptor gene, were found not only in SBMA patients but also in female carriers. Conclusions Leukocyte mtDNA copy number, mtDNA ∆CT and mtDNA 4977 may serve as useful biomarkers of mtDNA damage and can be used to monitor SBMA disease progression.