Abstract
Leber hereditary optic neuropathy (LHON) is primarily caused by pathogenic mitochondrial DNA (mtDNA) variants, most commonly the m.11778G>A variant in the MT-ND4 gene. The presence of this variant alone is insufficient to trigger disease symptoms, of which vision loss is the hallmark. Given the incomplete penetrance and inter-population variability in modifying factors, this study aimed to investigate two previously proposed genetic risk factors for LHON in the Polish population. Using quantitative PCR, we measured the mtDNA copy number in peripheral blood of affected and unaffected carriers of the m.11778G>A variant. In addition, we assessed the frequency of the PRICKLE3 c.157C>T variant in symptomatic, asymptomatic and control individuals using PCR-RFLP. Our results indicate that mtDNA copy number was not associated with LHON symptom manifestation in the Polish cohort under conditions tested, in contrast to previously reported associations in other populations. In addition, the PRICKLE3 c.157C>T variant was absent in our cohort, indicating that it is not a common modifier of LHON penetrance in the Polish population. These findings suggest that the incomplete penetrance of LHON in the Polish population may involve other modifying factors, such as yet unidentified nuclear DNA variants.