Investigation on mtDNA deletions and twinkle gene mutation (G1423C) in Iranian patients with chronic progressive external opthalmoplagia

Background: Chronic progressive external ophthalmoplagia (CPEO) is a phenotypic mitochondrial disorder that affects external ocular and skeletal muscles and is associated with a single or multiple mitochondrial DNA (mtDNA) deletions and also nuclear gene mutations. There are also some reports about the relationship between CPEO and the nuclear Twinkle gene which encodes a kind of mitochondrial protein called Twinkle.
Aims: To study the mtDNA deletions and Twinkle gene G1423C point mutation in Iranian patients with CPEO.
Materials and Methods: We collected 23 muscle samples from patients with CPEO, 9 women (mean age 34.3 years) and 14 men (36.7 years). Multiplex polymerase chain reaction (PCR) method was used to find the presence of single or multiple deletions in mtDNA. Single stranded conformational polymorphism (SSCP) and restriction fragment length polymorphism (PCR-RFLP) methods were carried out to investigate point mutation (G1423C) in the Twinkle gene in all DNA samples.
Results: Different sizes of mtDNA deletions were detected in 16 patients (69.6%). Each of the 5.5, 7, 7.5 and 9 kb deletions existed only in 1 patient. Common deletion (4977bp) and 8 kb deletion were detected in 5 and 3 patients respectively. Multiple deletions were also present in 4 patients. Out of 23 patients included in our study, two cases (8.7%) had Twinkle gene mutation (G1423C) and 5 patients (21.7%) did not show any deletions in mtDNA or the Twinkle gene mutation.
Conclusion: Our study provides evidence that the investigation of mtDNA and Twinkle gene mutations in CPEO may help with early diagnosis and prevention of the disease. Patients who did not show deletions in the mtDNA or G1423C mutation in the Twinkle gene may have other mtDNA, Twinkle or nuclear gene mutations.