Malattia leventinee: refinement of the genetic locu and phenotypic variability in autoomal dominant macular druen Original Reearch Article

PURPOE: To tudy the phenotypic variability in patient inheriting the dieae gene for malattia leventinee (dominant macular druen) and refine the localization of the gene. METHOD: A family with dominant radial druen wa acertained and tudied with clinical examination and DNA linkage analyi. Inheritance of the dieae gene wa determined by DNA analyi and ued to document the variability in phenotypic expreion. REULT: Fifty family member were tudied with fundu photography and genotyping. Linkage analyi howed that the dieae in thi family wa linked to chromoome 2p16-21 with a maximum lod core of 3.72 at D22153. An affected patient with obligate recombination allowed refinement of the dieae interval to a 6.2-cM region between D22227 and D2378. The phenotype of older affected patient varied from evere geographic atrophy or ubretinal fibroi to a ingle drue adjacent to the optic dik. mall and medium-ized, nonradial, and oft macular druen een in four older individual in the family were not pecifically aociated with the dieae haplotype. CONCLUION: Refinement of the localization of the gene for malattia leventinee will facilitate it poitional cloning. Genotypic documentation of the variable expreion of the dieae how that a ingle, large, ubretinal drue adjacent to the optic dik i conitent with inheritance of the dieae gene. oft macular druen in low abundance were not pecifically aociated with inheritance of the dieae gene. Thee reult will facilitate the genetic couneling of patient with malattia leventinee. It i unknown what proportion of age-related macular degeneration arie from mutation in dieae gene for dominant druen.