Mitochondrial Copy Number and D-Loop Variants in Pompe Patients

Document Type : Original Article


1 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Medical Genetic, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

3 Department of Pediatric Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 4Iranian Center for Neurological Research, Tehran University of Medical Sciences, Tehran, Iran


Pompe disease is a rare neuromuscular genetic disorder and is classified into two forms of early and late-onset. Over the past two decades, mitochondrial abnor- malities have been recognized as an important contributor to an array of neuromuscular diseases. We therefore aimed to compare mitochondrial copy number and mitochondrial displacement-loop sequence variation in infantile and adult Pompe patients.
Materials and Methods
In this retrospective study, the mitochondrial D-loop sequence was analyzed by polymerase chain reaction (PCR) and direct sequencing to detect pos- sible variation in 28 Pompe patients (17 infants and 11 adults). Results were compared with 100 healthy controls and sequences of all individuals were compared with the Cam- bridge reference sequence. Real-time PCR was used to quantify mitochondrial DNA copy number.
Among 59 variants identified, 37(62.71%) were present in the infant group, 14(23.333%) in the adult group and 8(13.333%) in both groups. Mitochondrial copy number in infant patients was lower than adults (P < 0.05). A significant frequency differ- ence was seen between the two groups for 12 single nucleotide polymorphism (SNP). A novel insertion (317-318 ins CCC) was observed in patients and six SNPs were iden- tified as neutral variants in controls. There was an inverse association between mito- chondrial copy number and D-loop variant number (r=0.54).
The 317-318 ins CCC was detected as a new mitochondrial variant in Pompe patients.