Role of mitochondria in Ataxia-Telangiectasia:Investigation of mitochondrial deletions and Haplogroups

AbstractAtaxia-Telangiectasia (AT) is a rare human neurodegenerativeautosomal recessive multisystem disease that is characterizedby a wide range of features including, progressivecerebellar ataxia with onset during infancy, occulocutaneoustelangiectasia, susceptibility to neoplasia, occulomotor disturbances,chromosomal instability and growth and developmentalabnormalities. Mitochondrial DNA (mtDNA) has theonly non-coding regions at the displacement loop (D-loop)region that contains two hypervariable segments (HVS-I andHVS-II) with high polymorphism. We investigated mt-DNAdeletions and haplogroups in AT patients. In this study, 24Iranian patients suffering from AT and 100 normal controlswere examined. mt-DNA was extracted from whole bloodand examined by 6 primers for existence of mitochondrialdeletions. We also amplified and sequenced the mtDNAHVS-I by standard sequencing techniques. mtDNA deletionswere observed in 54.1% (13/24) of patients (8.9 kb deletionin all samples, 5.0 kb in one and 7.5 kb in two patients), representingmtDNA damage which may be due to oxidativestress in mitochondria. Our results showed that there is noassociation between mtDNA haplogroups and AT. This datamay indicate involvement of mitochondrial damage in thepathogenesis of AT.