MALATTIA LEVENTINESE - REFINEMENT OF THE GENETIC-LOCUS AND PHENOTYPICVARIABILITY IN AUTOSOMAL-DOMINANT MACULAR DRUSEN

PURPOSE: To study the phenotypic variability in patients inheriting th e disease gene for malattia leventinese (dominant macular drusen) and refine the localization of the gene. METHODS: A family with dominant r adial drusen was ascertained and studied with clinical examination and DNA linkage analysis. Inheritance of the disease gene was determined by DNA analysis and used to document the variability in phenotypic exp ression. RESULTS: Fifty family members were studied with fundus photog raphy and genotyping. Linkage analysis showed that the disease in this family was linked to chromosome 2p16-21 with a maximum lod score of 3 .72 at D2S2153. An affected patient with obligate recombinations allow ed refinement of the disease interval to a 6.2-cM region between D2S22 27 and D2S378. The phenotype of older affected patients varied from se vere geographic atrophy or subretinal fibrosis to a single druse adjac ent to the optic disk. Small and medium sized, nonradial, and soft mac ular drusen seen in four older individuals in the family were not spec ifically associated with the disease haplotype. CONCLUSIONS: Refinemen t of the localization of the gene for malattia leventinese will facili tate its positional cloning. Genotypic documentation of the variable e xpression of the disease shows that a single, large, subretinal druse adjacent to the optic disk is consistent with inheritance of the disea se gene. Soft macular drusen in low abundance were not specifically as sociated with inheritance of the disease gene. These results will faci litate the genetic counseling of patients with malattia leventinese. I t is unknown what proportion of age-related macular degeneration arise s from mutations in disease genes for dominant drusen. (C) 1998 by Els evier Science Inc. All rights reserved.