Autosomal dominant macular at 6q14 excludes CORD7 and MCDR1/PBCRA loci

PURPOSE. Localization of the gene responsible fur autosomal dominant atroph ic macular degeneration (adMD) in a large pedigree UM:H785. METHODS. Standard ophthalmologic examinations were performed. Microsatellit e markers were used to map the disease gene by linkage and haplotype analys es. RESULTS. The macular degeneration in this family is characterized by progre ssive retinal pigment epithelial atrophy in the macula without apparent per ipheral involvement by ophthalmoscopy or functional studies. Acuity loss pr ogressed with age and generally was worse in the older affected individuals . The rod and cone function remained normal or nearly normal in all tested affected members up to 61 years of age. The phenotype in our family has cha racteristics similar to Stargardt-like macular degeneration with some diffe rences. Haplotype analysis localized the disease gene in our adMD family to an 8-cM region at 6q14. which is within the 18-cM interval of STGD3 but ex cludes cone-rod dystrophy 7 (CORD7; centromeric) and North Carolina macular degeneration and progressive bifocal chorioretinal atrophy (MCDR1/PBCRA; t elomeric). The mapping interval overlaps with that of recessive retinitis p igmentosa (RP25). CONCLUSIONS. These results implicate at least three genetically distinct lo ci for forms of macular degeneration that lie within a 30-cM interval on ch romosome 6p-11-6q16: CORD7, adMD, and MCDR1/PBCRA. Because the critical int erval for the adMD family studied overlaps with STGD3 and RP25, these loci could be allelic.