mitochondrial variants in pompe disease: a comparison between classic and non-classic forms

Objective: pompe disease (pd) is a progressive neuromuscular disorder that is caused by glucosidase acid alpha (gaa) deleterious mutations. mitochondrial involvement is an important contributor to neuromuscular diseases. in this study the sequence of mt-atp 6/8 and cytochrome c oxidase i/ii genes along with the expression levels of the former genes were compared in classic and non-classic patients. materials and methods: in this case-control study, the sequence of mt-atp 6/8 and cytochrome c oxidase was analyzed by polymerase chain reaction (pcr)-sanger sequencing and expression of mt-atp genes were quantified by real time-pcr (rt-pcr) in 28 pompe patients. the results were then compared with 100 controls. all sequences were compared with the revised cambridge reference sequence as reference. results: screening of mt-atp6/8 resulted in the identification of three novel variants, namely t9117a, a8456c and a8524c. there was a significant decrease in mt-atp6 expression between classic (i.e. adult) and control groups (p=0.030). additionally, the mt-atp8 expression was significantly decreased in classic (p=0.004) and non-classic (i.e. infant) patients (p=0.013). in total, 22 variants were observed in cytochrome c oxidase, five of which were nonsynonymous, one leading to a stop codon and another (c9227g) being a novel heteroplasmic variant. the a8302g in the lysine trna gene was found in two brothers in a pedigree, while a t7572c variant in the aspartate trna gene was observed in two brothers in another pedigree. conclusion: the extent of mitochondrial involvement in the classic group was more significant than in the non-classic form. beside gaa deleterious mutations, it seems that mtdna variants have a secondary effect on pd. understanding, the role of mitochondria in the pathogenesis of pompe may potentially be helpful in developing new therapeutic strategies.