Mitochondrial DNA analysis as a diagnostic tool in singleton cases of Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON) is characterized by subacute loss of central vision due to bilateral optic nerve atrophy accompanied by several nonspecific clinical findings. The only pathognomonic feature is its strictly maternal inheritance. It was therefore impossible to establish the diagnosis in patients with no known affected matrilinear sibs, until several mutations in the mitochondrial DNA (mtDNA) were discovered in relation to LHON. The authors describe the case histories and the occurrence of six mtDNA mutations in eight presumed singleton LHON patients and discuss the clinical and genetic implications of the results.