A mutation of mitochondrial DNA in Japanese families with Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease characterized by optic nerve degeneration associated with severe bilateral visual loss in young men and occasionally in women. A mitochondrial DNA (mtDNA) replacement mutation in LHON patient, G to A transition at nucleotide position (nt) 11778 converting the 340th arginine to histidine in the NADH dehydrogenase subunit 4, was detected as SfaNI site polymorphism (Wallace et al., Science, 242: 1427-1430, 1988). To evaluate if the SfaNI site loss can be used to diagnose LHON patients, mtDNAs from peripheral blood of six affected males including five probands from five unrelated Japanese families with LHON, a pair of parents and a normal sister of one of the probands and 4 control persons were analyzed using PCR amplification method. The mutation of leukocyte mtDNA at nt 11778 was identified in all of the affected patients, the normal mother and the sister examined, while the father who is normal and 4 control persons did not show the change. These findings support that the mutation at nt 11778 is also associated with LHON in the Japanese and the test of the SfaNI site loss described here is useful for confirming the clinical diagnosis of LHON patients with the mutation at nt 11778.