Genetic counseling in Leber hereditary optic neuropathy (LHON).

Purpose: To demonstrate the importance of mitochondrial DNA (mtDNA) analysis in the diagnosis of Leber hereditary optic neuropathy (LHON) and illustrate the difficulties in genetic counseling of the disease.

Participants And Methods: Ophthalmological and molecular genetic study of one affected and three unaffected members from a family with heteroplasmic ND1/3460 mtDNA mutation associated with LHON.

Results: The proband had variable amounts of mutant mtDNA in all his tissues studied, ranging from 58% in blood to 92% in subcutis. The mother had an extremely low amount of mutant mtDNA in her tissues, except for hair roots, which contained only normal mtDNA. No mutant mtDNA could be detected in the proband's unaffected sister and maternal aunt.

Conclusions: Despite her minimal mutation load, the mother of the proband has still transmitted a considerable amount of mutant mtDNA to her son, who is severely affected. Although proband's unaffected sister and maternal aunt had no mutant mtDNA, a theoretical risk that they may transmit the disease to their offspring cannot be excluded.