ABSTRACT
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