Peripherin/RDS and VMD2 mutations in macular dystrophies with adult-onset vitelliform lesion

PURPOSE: Adult-onset vitelliform macular dystrophy (AVMD) is a pleomorphic late-onset macular phenotype characterized by a central yellow deposit between the neural retina and retinal pigment epithelium. Mutations in the genes encoding peripherin/RDS and VMD2 have been previously reported in some subjects with AVMD. The purpose of this investigation was to determine the prevalence of mutations in these two genes in a cohort of cases with macular dystrophies presenting with vitelliform lesions in adulthood. METHODS: Fifty nine consecutively ascertained and unrelated subjects prospectively coded as pattern or vitelliform macular dystrophies were reviewed and twelve subjects with a vitelliform lesion were identified. Patient evaluation included comprehensive ocular examination, retinal imaging, and functional studies in selected subjects. The RDS and VMD2 genes were screened for variation by direct DNA sequencing of coding regions and intron/exon boundaries. RESULTS: Twenty-two DNA sequence variants were identified in the genes encoding RDS and VMD2. A Pro210Arg variant found in the RDS gene of one subject was the only definite mutation detected in either gene. CONCLUSIONS: The Pro210Arg mutation has been reported previously in patients with pattern dystrophy confirming the observation that pattern dystrophy can present with an AVMD phenotype. Although RDS and VMD2 are the only known genes with mutations contributing to AVMD, our series demonstrates that most patients have mutations in genes that have yet to be discovered.