Leber's hereditary optic neuropathy mutations in 31 Spanish individuals affected by optic atrophy; segregation studies in 5 families

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a mitochondrial d isorder that represents the most frequent cause of visual loss among otherw ise healthy young men. PATIENTS AND METHODS: We have screened for the most important LHON mutation s (primary mutations) and several other previously described mutations (sec ondary mutations) in 31 Spanish patients suffering from optic atrophy. Thes e individuals fulfilled the clinical criteria for LHON. We have compared th e mutation frequencies obtained with those reported in several other countr ies. We have also followed the segregation of the disease and its associate d LHON mutations in five families. The screening has been performed by PCR followed by restriction enzyme digestions and electrophoretic separation. RESULTS: 67.75% of the patients did not harbour any of the studied mutation s, whereas 16.13% showed one mutation and the remaining 16.13% carried two Leber mutations in their mitochondrial DNA. The three primary mutations as well as G15257A were the changes most frequently detected (30% each of them ). There were no significant differences among the compared populations in terms of frequencies of the primary mutations. In contrast, our patients sh owed a significantly higher rate of 15257 mutation. CONCLUSIONS: The incidence of primary LHON mutations among the Spanish pati ents is not statistically different from those observed in other Caucasian populations. Transmission of the mutation to the progeny is not necessarily linked to the transmission of the disease. This fact complicates genetic c ounselling and makes prenatal diagnosis almost impossible for this disease.