[Correlation between clinical and molecular genetic findings in Leber's optic atrophy]

Leber's hereditary optic neuropathy (LHON) is associated with point mutations of mitochondrial DNA (mtDNA) that appear to be pathogenetic for this disease. These mutations affect nucleotide positions 3460, 4160, 11,778, 14,484, and possibly 15,257. The pathogenetic significance of other mtDNA point mutations (secondary mutations) is less clear. We reviewed the clinical and molecular genetic characteristics of 29 visually symptomatic patients from 26 families. In addition, we studied 54 relatives of the maternal line of these patients. Sixteen of them underwent clinical and molecular genetic examination; 38 underwent only molecular genetic examination. The 29 affected individuals showed a male predominance of 93.1% (27/29) and ages of onset of visual loss ranging from 15 to 55 years. The time interval between affected eyes was never longer than 1 year. Tobacco and/or alcohol abuse was common. Peripapillary microangiopathy was found in 20.7% (6/29) of our patients. The number of patients with peripapillary microangiopathy seems to be small, but we could not examine all patients early after onset of the disease: the time of first examination is critical for the diagnosis of peripapillary microangiopathy. From the 16 relatives who underwent clinical examination, 62.5% (10/16) also had peripapillary microangiopathy. Eighteen patients were analyzed by brain computed tomography or magnetic resonance imaging. Four definitely pathological results seem remarkably high in comparison with the results of other authors. Our LHON patients and their relatives invariably had an identical pattern of point mutations, both primary as well as secondary. Of the LHON patients, 79.3% had the primary mutation at position 11,778, 20.7% at position 3460. Different numbers and combinations of secondary mutations were observed in a large portion of both groups. Three patients with the 11,778 mutation noticed remarkable visual recovery. There was no clear correlation between the type and number of point mutations in the individual and the severity of the disease.