CLINICAL-FEATURES OF A STARGARDT-LIKE DOMINANT PROGRESSIVE MACULAR DYSTROPHY WITH GENETIC-LINKAGE TO CHROMOSOME 6Q

Background and Objectives: We identified a large family affected with a macular dystrophy whose main clinical features are similar to those of Stargardt's disease. Unlike true Stargardt's disease, the disorder in this family is inherited in an autosomal dominant fashion. We sough t to identify the chromosomal location of the disease-causing gene and to clinically define the phenotype in a number of affected family mem bers. Methods: Thirty-two family members underwent clinical examinatio n. A total of 23 affected family members were identified, and these pa tients were genotyped at candidate loci with short tandem repeat polym orphisms. The LINKAGE computer program was used for linkage calculatio ns. Results: Affected patients had normal vision in early childhood bu t began to experience difficulty with central vision between 5 and 23 years of age. Fundus examination early in the disease course revealed flecks in the macula. Central atrophy developed later, with visual acu ity decreasing to 20/200 or worse in all patients older than 31 years. Fluorescein angiography revealed no evidence of choroidal silence. El ectroretinograms were near normal in younger affected individuals and were most notable for prolonged implicit times in a 73-year-old patien t. Chromosome linkage analysis revealed the disease-causing gene to be located near the centromere on the long arm of chromosome 6. The maxi mum lod score was 5.5 (theta=0) with marker D6S280. Multipoint analysi s resulted in a peak lod score of 6.2 in the interval between markers D6S313 and D6S252 and excluded the interval containing the North Carol ina macular dystrophy gene. Conclusions: This autosomal dominant macul ar dystrophy is clinically similar to Stargardt's disease, with the ex ception of its pattern of inheritance. The clearly progressive nature of the disease distinguishes it from North Carolina macular dystrophy, whose causative gene is also located on the long arm of chromosome 6. Identification of the gene involved in this disease may provide clues to the pathogenesis of age-related-macular degeneration.