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

• Published in: Ophthalmology (Rochester, Minn.) Vol. 108; no. 11; p. 2060
• Main Authors: Seddon, J M, Afshari, M A, Sharma, S, Bernstein, P S, Chong, S, Hutchinson, A, Petrukhin, K, Allikmets, R
• Format: Journal Article
• Language: English
• Published: United States 01-11-2001
• Subjects: Aged; Bestrophins; Chloride Channels; DNA Mutational Analysis; Electrooculography; Eye Proteins - genetics; Female; Fluorescein Angiography; Fundus Oculi; Genotype; Humans; Macular Degeneration - genetics; Male; Middle Aged; Mutation; Pedigree; Phenotype; Visual Acuity
• ISSN: 0161-6420
• DOI: 10.1016/S0161-6420(01)00777-1

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.
Case-comparison study of phenotype-genotype correlations.
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.
Presence of mutations in the Best gene (VMD2; OMIM 153700) and the clinical phenotype.
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; T216I), 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).
Novel mutations in the VMD2 gene were found in patients 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.