Leber hereditary optic neuropathy (LHON) exhibits maternal inheritance. The primary mitochondrial DNA mutation responsible for >90% of LHON cases are point mutations at positions:
- A 11778 (ND4), 3460 (ND1), and 14484 (ND6) in mitochondrial genes encoding Complex I subunits ✓
- B 3243 (tRNA-Leu) and 8344 (tRNA-Lys) causing MELAS and MERRF
- C 4216 and 13708 (secondary mutations affecting disease penetrance)
- D POLG1 nuclear gene encoding mitochondrial DNA polymerase
Explanation
The three primary LHON mutations are: G11778A in ND4 (most common, ~70% of cases, worst prognosis), G3460A in ND1 (~15%), and T14484C in ND6 (~15%, best spontaneous recovery rate up to 50%). All three affect Complex I (NADH dehydrogenase) subunit genes, impairing mitochondrial oxidative phosphorylation and increasing reactive oxygen species (ROS). Retinal ganglion cells of the papillomacular bundle are preferentially affected due to high energy demand. Idebenone (INN: Raxone) is approved in Europe for LHON treatment within 1 year of vision loss onset — a mitochondrial antioxidant bypassing Complex I. Gene therapy (lenadogene nolparvovec) is under trial.
Reference: Khurana Comprehensive Ophthalmology, 7th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.