Leber's hereditary optic neuropathy (LHON) is caused by mitochondrial DNA mutations. The most common primary mutation accounting for approximately 70% of LHON cases in European populations is at position:

• A mtDNA position 14484 (ND6 gene)
• B mtDNA position 3460 (ND1 gene)
• C mtDNA position 11778 (ND4 gene) ✓
• D mtDNA position 15257 (cytochrome b gene)

Explanation

The G11778A mutation in the ND4 subunit of Complex I accounts for approximately 50–70% of LHON cases worldwide and 70% in European populations. The 14484 mutation (ND6) has the best prognosis for spontaneous recovery. The 3460 mutation (ND1) accounts for ~10–15%. All three primary mutations affect Complex I of the electron transport chain, impairing mitochondrial respiration specifically in retinal ganglion cells, which are particularly vulnerable due to their high energy demands in the unmyelinated optic fiber layer.

Reference: Khurana Comprehensive Ophthalmology, 7th ed.

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Written and medically reviewed by the StethoPrep medical team.