Clinical correlation of mitochondrial DNA heteroplasmy and Leber's hereditary optic neuropathy.

Mitochondrial DNA (mtDNA) was studied in a Japanese family with two male siblings who were affected with Leber's hereditary optic neuropathy. The polymerase chain reaction (PCR) products of blood mtDNA from the affected siblings, the obligate carrier mother and a possible carrier sister showed abnormal restriction sites for endonucleases SfaNI and Mae III that were compatible with the Wallace mutation at nucleotide position 11,778 base pair of mtDNA, whereas PCR products from the father and controls had normal restriction sites. In addition to the mutant mtDNA, these family members had normal mtDNA that was revealed more obviously in Mae III-digested samples, indicating heteroplasmy consisting of a mixture of mutant and normal mtDNA. The affected siblings showed a marked difference in visual outcome during the 6-year follow-up, and the severity of optic nerve involvement appeared to be correlated with the relative proportion of mutant mtDNA.