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- Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease of the optic nerve. The disease can develop in individuals from 6 to 60 years old (mean age of onset is 27 years).
- In a form of the disease accounting for 50% of cases, the mutation was a substitution in the mitochondrial gene, ND4, for an NADH dehydrogenase subunit. The mutation changes an arginine to a histidine codon and a SfaNI to a MaeI site.
- In other forms of the disease, substitution mutations occur in ND1, ND2, ND5, CYB and ATP6 genes.
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- Deletions of parts of human mitDNA have also been observed. These are associated with ocular myopathy and Pearson marrow/pancreas syndrome.
- Two parts of the mitochondrial DNA are never missing from DNA of diseased mitochondria. These correspond to the origins of leftward and rightward replication.
- Most cases are new mutations (not inherited from parents).
- The mitochondria of affected individuals gradually change from heteroplasmy to homoplasmy as the individual ages.
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- A change in the mitochondrial gene for the lysine-carrying tRNA is positively correlated with MERRF in 3 family pedigrees and is absent in 75 control families.
- Affected individuals are heteroplasmic, as are some healthy individuals in the same families. There is an age-related association of genotype and phenotype.
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