Biallelic Variants in Respiratory Chain Complex-I Genes Lead to Isolated or Syndromic Inherited Optic Neuropathy

The mitochondrial complex I (CI) is the major entry point for electrons to the respiratory chain, essential in energy metabolism.Mutations in both mitochondrial or nuclear genes lead to CI deficiency, a phenotypically heterogeneous mitochondrial disease. Particularly, mutations of nuclear genes encoding CI subunits or assembly factors are implicated. Most patients with nuclear determined CI deficiency show more severe mitochondrial disorder with or without visual loss. To date, there are limited reports of isolated optic atrophy (OA) due to pathogenic variants in nuclear genes important for CI function.