Linkage study of Best's vitelliform macular dystrophy (VMD2) in a large North American family

Best's vitelliform macular dystrophy (VMD2) is an autosomal dominant retinal dystrophy for which the underlying biochemical cause is unknown. We used 11 genetic markers in the vicinity of the VMD2 gene in our study of a large North American family in which macular dystrophy characteristics overlap the broad definition of Best's disease. Significant evidence for linkage was found for markers D11S956 (Z = 5.88, theta = 0.04) and FCER1B (Z = 4.31, theta = 0.00). Recombination events localized the disease gene to the 5-cM interval D11S956-UGB, a genetic inclusion interval that substantially overlaps the VMD2 inclusion interval defined by recombinants at FCER1B and UGB observed by other research groups. The resulting exclusion of ROM1 from the genetic inclusion interval eliminates ROM1 defects as a possible cause of the disease in this family. Linkage studies of many families, including those that share most but not all features with classical Best's disease, will be needed to properly evaluate genetic heterogeneity and the range of phenotypic variation that can result from VMD2 defects.