LINKAGE STUDY OF BESTS VITELLIFORM MACULAR DYSTROPHY (VMD2) IN A LARGE NORTH-AMERICAN FAMILY

Best's vitelliform macular dystrophy (VMD2) is an autosomal dominant r etinal dystrophy for which the underlying bio-chemical cause is unknow n. We used 1 1 genetic markers in the vicinity of the VMD2 gene in our study of a large North American family in which macular dystrophy cha racteristics overlap the broad definition of Best's disease, Significa nt evidence for linkage was found for markers D11S956 (<(Z) over cap> = 5.88, <(theta) over cap> = 0.04) and FCER1B (<(Z) over cap> = 4.31, <(theta) over cap> = 0.00). Recombination events localized the disease gene to the 5-cM interval D11S956-UGB, a genetic inclusion interval t hat substantially overlaps the VMD2 inclusion interval defined by reco mbinants at FCER1B and UGB observed by other research groups. The resu lting exclusion of ROM1 from the genetic inclusion interval eliminates ROM1 defects as a possible cause of the disease in this family. Linka ge studies of many families, including those that share most but not a ll features with classical Best's disease, will be needed to properly evaluate genetic heterogeneity and the range of phenotypic variation t hat can result from VMD2 defects.