Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland.

We have performed an entire-population-based survey of the epidemiology and penetrance of Leber hereditary optic neuropathy (LHON) in Finland - a country that is among the best-studied genetic isolates in the world. During our long-term clinical follow-up period since 1970, we have so far identified 36 LHON families in Finland, comprised of almost 1000 family members. Counting the unaffected family members has been possible thanks to accessible genealogical records, and this has improved the accuracy of our penetrance figures by minimizing the sample bias. Our results, although confirming some well-known features of LHON, indicate that the overall penetrance of LHON is lower than previously estimated, and that affected females have a higher incidence of affected offspring compared to the unaffected females. The prevalence of LHON in Finland is 1:50 000, and one in 9000 Finns is a carrier of one of the three LHON primary mutations.

Dominant optic atrophy: correlation between clinical and molecular genetic studies.

PURPOSE: To assess the clinical picture and molecular genetics of 14 Finnish families with dominant optic atrophy (DOA). METHODS: The clinical status of family members was based on the assessment of visual acuity, colour vision, visual fields and optic nerve appearance; 31 individuals were affected, two suspect and 21 unaffected. A total of 30 coding exons and exon- intron boundaries of the OPA1 gene were sequenced in order to detect mutations. RESULTS: Half the patients were diagnosed at the age of < or = 20 years. Ten out of 20 affected individuals followed up for > or = 6 years had a progressive disease and 10 had a stable disease. According to WHO criteria, 36% of the affected patients were visually handicapped. Eight OPA1 pathogenic mutations, all but one novel, and 18 neutral polymorphisms were detected. CONCLUSION: The most sensitive indicators of DOA were optic disc pallor and dyschromatopsia. With molecular genetic analysis, asymptomatic mutation carriers and DOA cases with a mild clinical outcome were ascertained. No mutational hotspot or Finnish major mutation in the OPA1 gene could be demonstrated as most families carried a unique mutation. No obvious genotype- phenotype correlation could be detected. Detailed clinical assessment and exclusion of non-DOA families prior to mutation screening are necessary for obtaining a high mutation detection rate.