Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration

Recently, the VMD2 gene has been identified as the causative gene in juveni le-onset vitelliform macular dystrophy (Best disease), a central retinopath y primarily characterised by an impaired function of the retinal pigment ep ithelium. In this study we have further characterised the spectrum of VMD2 mutations in a series of 41 unrelated Best disease patients. Furthermore we expanded our analysis to include 32 unrelated patients with adult vitellif orm macular dystrophy (AVMD) and 200 patients with age-related macular dege neration (AMD). Both AVMD and AMD share some phenotypic features with Best disease such as abnormal subretinal accumulation of lipofuscin material, pr ogressive geographic atrophy and choroidal neovascularisation, and may be t he consequence of a common pathogenic mechanism. In total, we have identifi ed 23 distinct disease-associated mutations in Best disease and four differ ent mutations in AVMD. Two of the mutations found in the AVMD patients were also seen in Best disease suggesting a considerable overlap in the aetiolo gy of these two disorders. There were no mutations found in the AMD group. In addition, four frequent intragenic polymorphisms did not reveal allelic association of the VMD2 locus with AMD. These data exclude a direct role of VMD2 in the predisposition to AMD.