Modifier variants in metabolic pathways are associated with an increased penetrance of Leber's Hereditary Optic Neuropathy.

ABSTRACT: Leber's hereditary optic neuropathy (LHON) is a debilitating mitochondrial disease characterised by bilateral painless vision loss. Despite being the most prevalent mitochondrial disorder, the precise pathophysiological mechanisms underlying the penetrance of LHON remain poorly understood. Nuclear modifier genes have been long suspected to affect phenotype-severity, however, specific cellular pathways implicated in the disease penetrance have been only suggested recently. In recent years, autosomal recessive variants in nuclear genes involved in complex I function and metabolic pathways were recognised to cause a typical LHON phenotype. This was proposed as a new autosomal recessive disease mechanism for LHON (arLHON). The association between nuclear variants and the LHON phenotype makes t

SUBMITTER: Arany ES 

PROVIDER: S-EPMC12859036 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature