Prevalence of primary mutations in Leber hereditary optic neuropathy: A five-year report from a tertiary eye care center in India.

Purpose: Genetic testing for primary mutations m.3460G>A, m.11778G>A, and m.14484T>C in ND1, ND4, and ND6 genes of mitochondrial DNA is the recommended assay for Leber hereditary optic neuropathy (LHON; OMIM 535000). This report discusses the outcome of molecular genetic screening for these three primary mutations in suspected LHON cases in India.

Methods: Two hundred and seventy-eight unrelated presumed LHON patients who were seen at the neuro-ophthalmology clinic of a tertiary eye care center from 2014-2018 were analyzed. They were genotyped for the three common variants by polymerase chain reaction-based direct sequencing, and their plasmy status was also determined by restriction enzyme digestion.

Results: Eighty two of 278 patients were positive for one of the 3 common mutations with m.11778G>A in ND4 gene more frequently distributed (N=72) in homoplasmic state (N=59/82). The mean onset age of visual loss was 21.1years (SD, 9.8 years; range, 5-58 years) in patients harboring the primary mutation. The most common clinical presentation was bilateral sequential painless vision loss with central and cecocentral scotomas in the visual field due to optic disc atrophy.

Conclusions: The study subjects are a sample of a much larger number of suspected LHON cases tested for primary mutations in India. (N= 278) and 29.4% (82/278) of patients harbour one of the 3 common mutations. Screening the entire mitochondrial genome and the other nuclear genes encoding mitochondrial protein, would probably aid in identifying the other less common mtDNA mutations causing LHON in Indian population.