Analysis of genetic risk factors for Leber hereditary optic neuropathy in the Polish population

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 neither mtDNA copy number nor the presence of the PRICKLE3 variant is associated with LHON symptom manifestation in the Polish cohort under conditions tested, in contrast to previously reported associations in other populations. 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. Research highlightsO_LIMitochondrial DNA (mtDNA) copy number and the presence of the c.157C>T variant in the PRICKLE3 gene do not influence the manifestation of Leber hereditary optic neuropathy (LHON) symptoms in the Polish population. C_LIO_LIThe results support a geographic dependence of genetic risk factors affecting the penetrance of LHON-associated mtDNA variants. C_LI