Risk Factors Associated With Leber Hereditary Optic Neuropathy due to Rare Mutations in Mitochondrial DNA-Encoded Respiratory Complex I Subunits

Clin Genet. 2024 Dec 23. doi: 10.1111/cge.14683. Online ahead of print.

Abstract

An in-depth analysis of susceptibility factors modifying the penetrance of rare Leber hereditary optic neuropathy-causing mutations in respiratory complex I genes encoded in mitochondrial deoxyribonucleic acid has not been performed. To bridge this gap, we conducted a review of the literature on rare mutations associated with LHON, selected those with substantial evidence of pathogenicity, and performed an in-depth analysis of the various pedigrees. Examining the influences that modify the penetrance of the classical mutations associated with this disease may offer insights into susceptibility factors in individuals carrying the rare mutations.

Keywords: Leber hereditary optic neuropathy; incomplete penetrance; mitochondrial deoxyribonucleic acid; rare mutation; respiratory complex I genes.