Abstract
PURPOSE. We investigated whether a group of patients with keratoconus (KTCN) harbor mutations in the mitochondrial genome.
METHODS. We sequenced the full mitochondrial genome in a group of Saudi patients with KTCN (n = 26) and 100 ethnically matched controls who had no KTCN by examination.
RESULTS. A total of 10 KTCN patients (38.5%) had potentially pathogenic nonsynonymous mtDNA mutations. Of the nonsynonymous sequence changes detected, 4 (40%) were in Complex I, one was in the tRNA(Glutamine), one was in tRNA(Tryptophan), one was in tRNA(Asparagine), one was in tRNA(Histidine), and two were in the tRNA(Leucine2). One nonsynonymous sequence change was heteroplasmic, whereas all the remaining 9 were homoplasmic. These sequence changes were not detected in controls of similar ethnicity. Four sequence changes were novel (were not reported previously) and 5 were reported previously. Additionally, we detected 54 synonymous (does not result in an amino acid change) sequence changes with no pathologic significance.
CONCLUSIONS. If our results are confirmed in a larger cohort and multiple ethnicities, then mtDNA mutation may be considered as a genetic risk factor contributing indirectly through the oxidative stress mechanism to the development and/or progression of KTCN.