Purpose: To assess the clinical picture and molecular genetics of 14 Finnish f amilies with dominant optic atrophy (DOA). Methods: The clinical status of famil y members was based on the assessment of visual acuity, c...Purpose: To assess the clinical picture and molecular genetics of 14 Finnish f amilies with dominant optic atrophy (DOA). Methods: The clinical status of famil y members was based on the assessment of visual acuity, colour vision, visual fi elds and optic nerve appearance; 31 individuals were affected, two suspect and 2 1 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 we re diagnosed at the age of ≤20 years. Ten out of 20 affected individuals follow ed up for ≥6 years had a progressive disease and 10 had a stable disease. Accor ding to WHO criteria, 36%of the affected patients were visually handicapped. Ei ght OPA1 pathogenic mutations, all but one novel, and 18 neutral polymorphisms w ere detected. Conclusion: The mos t sensitive indicators of DOA were optic disc pallor and dyschromatopsia. With m olecular genetic analysis, asymptomatic mutation carriers and DOA cases with a m ild clinical outcome were ascertained. No mutational hotspot or Finnish major mu tation 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 screen ing are necessary for obtaining a high mutation detection rate.展开更多
文摘Purpose: To assess the clinical picture and molecular genetics of 14 Finnish f amilies with dominant optic atrophy (DOA). Methods: The clinical status of famil y members was based on the assessment of visual acuity, colour vision, visual fi elds and optic nerve appearance; 31 individuals were affected, two suspect and 2 1 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 we re diagnosed at the age of ≤20 years. Ten out of 20 affected individuals follow ed up for ≥6 years had a progressive disease and 10 had a stable disease. Accor ding to WHO criteria, 36%of the affected patients were visually handicapped. Ei ght OPA1 pathogenic mutations, all but one novel, and 18 neutral polymorphisms w ere detected. Conclusion: The mos t sensitive indicators of DOA were optic disc pallor and dyschromatopsia. With m olecular genetic analysis, asymptomatic mutation carriers and DOA cases with a m ild clinical outcome were ascertained. No mutational hotspot or Finnish major mu tation 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 screen ing are necessary for obtaining a high mutation detection rate.
