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Leber's optic atrophy

From SNPedia

Leber optic atrophy, also known as Leber’s hereditary optic neuropathy (LHON),[1] is a mitochondrially inherited degeneration of retinal ganglion cells and their axons that leads to an acute or subacute loss of central vision, predominantly affecting young adult males. However, LHON is only transmitted through the mother as it is primarily due to mutations in the mitochondrial (not nuclear) genome and only the egg contributes mitochondria to the embryo.Wikipedia

LHON shows a very large amount of heterogeneity. The age of onset varies between 1-70 years of age, although 95% of patients have onset by their early 50's. There is incomplete penetrance, with only approximately 50% of the males and 10% of the females carrying a pathogenic mtDNA mutation actually developing the optic neuropathy. The estimated prevalence of the disorder is 1 in 30,000 in Northern Europe, and the estimated mutation carrier rate is 1 in 350.OMIM

According to MitoMap, 95% of all cases of Leber optic atrophy derive from one of just three mutations:

  • rs199476112, aka the R340H mutation in the MTND4 gene, seen in 69% of all LHON patients
  • rs199476118, aka the A52T mutation in the MTND1 gene, seen in 13% of patients
  • rs199476104, aka the M64V mutation in the MTND6 gene, seen in 14% of patients