[An analysis of 6 Leber mutations in 31 individuals with optic atrophy. A study of its transmission in 5 families]

Centre de Genètica Mèdica i Molecular, IRO, Hospital Duran i Reynals, Barcelona.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder that represents the most frequent cause of visual loss among otherwise healthy young men. PATIENTS AND METHODS: We have screened for the most important LHON mutations (primary mutations) and several other previously described mutations (secondary mutations) in 31 Spanish patients suffering from optic atrophy. These individuals fulfilled the clinical criteria for LHON. We have compared the mutation frequencies obtained with those reported in several other countries. We have also followed the segregation of the disease and its associated 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 mutations, 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 showed a significantly higher rate of 15257 mutation. CONCLUSIONS: The incidence of primary LHON mutations among the Spanish patients 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 counselling and makes prenatal diagnosis almost impossible for this disease.

PMID: 10220763 [PubMed - indexed for MEDLINE]