Assessment of mutations in the Best macular dystrophy (VMD2) gene in patients with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and bull's-eye maculopathy

Purpose: To study the presence, of Best macular dystrophy (VMD2) gene mutations in patients diagnosed with maculopathies other than; classic Best disease, and to describe the clinical characteristics of these subjects. Design. Case-comparison study of phenotype-genotype correlations. Methods. Patients with either age-related maculopathy (ARM; n = 259) or maculopathies other than classic, Best disease (n = 28) were screened for mutations in the Best gene (VMD2; OMIM 153700). These cases were compared with ethnically similar subjects in the same age range without maculopathy (n = 196). All patients underwent a complete dilated ocular examination, and all affected individuals underwent fundus photography. Phenotype-genotype comparisons were made. Main Outcome Measures; Presence of mutations, in the Best gene (VMD2; OMIM 153700) and the clinical phenotype. Results: Three of 259 patients (1%), with ARM and 2 of 28 patients (7%) with other maculopathies including 1 of 3 patients with adult-onset foveomacular vitelliform dystrophy and 1 of 5 patients with a bull's eye maculopathy, but none of the controls, were found to possess amino acid-changing variants in the VMD2 gene. These included a man with confluent drusen and retinal pigment epithelial detachments (variant in exon 6; T216l), a man with geographic atrophy and numerous soft drusen (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations resembling bull's-eye maculopathy (variant in exon 4; E119Q) and a woman diagnosed with adult-onset foveomacular vitelliform dystrophy (variant in; exon 4; A146K). Conclusions. Novel mutations in the VMD2. gene were found inpatients diagnosed with maculopathies other than classic Best disease. Some cases diagnosed as adult-onset vitelliform foveomacular dystrophy may represent a variant of Best disease with delayed onset. The VMD2 gene does not play a major role in the development of ARM. Ophthalmology 2001;108:2060-2067 (C) 2001 by the American Academy of Ophthalmology.