Mitochondrial Copy Number and D-Loop Variants in Pompe Patients.
OBJECTIVE
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.


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.


RESULTS
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).


CONCLUSIONS
The 317-318 ins CCC was detected as a new mitochondrial variant in Pompe patients.
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Fatemeh
F
Bahreini
Department of Medical Genetic, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Massoud
M
Houshmand
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Hossein
MH
Modaresi
Department of Pediatric Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hassan
H
Tonekaboni
Iranian Center for Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
Shahriar
S
Nafissi
Iranian Center for Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
Ferdoss
F
Nazari
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Seyed Mohammad
SM
Akrami
Copy Number; D-Loop; Mitochondrial DNA; Pompe