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

PURPOSE

Localization of the gene responsible for autosomal dominant atrophic macular degeneration (adMD) in a large pedigree UM:H785.

METHODS

Standard ophthalmologic examinations were performed. Microsatellite markers were used to map the disease gene by linkage and haplotype analyses.

RESULTS

The macular degeneration in this family is characterized by progressive retinal pigment epithelial atrophy in the macula without apparent peripheral involvement by ophthalmoscopy or functional studies. Acuity loss progressed 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 characteristics similar to Stargardt-like macular degeneration with some differences. 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 excludes cone-rod dystrophy 7 (CORD7; centromeric) and North Carolina macular degeneration and progressive bifocal chorioretinal atrophy (MCDR1/PBCRA; telomeric). The mapping interval overlaps with that of recessive retinitis pigmentosa (RP25).

CONCLUSIONS

These results implicate at least three genetically distinct loci for forms of macular degeneration that lie within a 30-cM interval on chromosome 6p11-6q16: CORD7, adMD, and MCDR1/PBCRA. Because the critical interval for the adMD family studied overlaps with STGD3 and RP25, these loci could be allelic.