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Allelic variation in the VMD2 gene in best disease and age-related macular degeneration
Journal article   Open access   Peer reviewed

Allelic variation in the VMD2 gene in best disease and age-related macular degeneration

Andrew J Lotery, Francis L Munier, Gerald A Fishman, Richard G Weleber, Samuel G Jacobson, Louisa M Affatigato, Brian E Nichols, Daniel F Schorderet, Val C Sheffield and Edwin M Stone
Investigative ophthalmology & visual science, Vol.41(6), pp.1291-1296
05/2000
PMID: 10798642
url
https://iovs.arvojournals.org/article.aspx?articleid=2123121View
Published (Version of record) Open Access

Abstract

To assess the allelic variation of the VMD2 gene in patients with Best disease and age-related macular degeneration (AMD). Three hundred twenty-one AMD patients, 192 ethnically similar control subjects, 39 unrelated probands with familial Best disease, and 57 unrelated probands with the ophthalmoscopic findings of Best disease but no family history were screened for sequence variations in the VMD2 gene by single-strand conformation polymorphism (SSCP) analysis. Amplimers showing a bandshift were reamplified and sequenced bidirectionally. In addition, the coding regions of the VMD2 gene were completely sequenced in six probands with familial Best disease who showed no SSCP shift. Forty different probable or possible disease-causing mutations were found in one or more Best disease or AMD patients. Twenty-nine of these variations are novel. Of the 39 probands with familial Best disease, mutations were detected in all 39 (33 by SSCP and 6 by DNA sequencing). SSCP screening of the 57 probands with a clinical diagnosis of Best disease but no family history revealed 16 with mutations. Mutations were found in 5 of 321 AMD patients (1.5%), a fraction that was not significantly greater than in control individuals (0/192, 0%). Patients with the clinical diagnosis of Best disease are significantly more likely to have a mutation in the VMD2 gene if they also have a positive family history. These findings suggest that a small fraction of patients with the clinical diagnosis of AMD may actually have a late-onset variant of Best disease, whereas at the same time, a considerable fraction of isolated patients with the ophthalmoscopic features of Best disease are probably affected with some other macular disease.
 Retinal Degeneration - diagnosis Retinal Degeneration - genetics Humans Male DNA Primers - chemistry Sequence Analysis, DNA Macular Degeneration - diagnosis Polymorphism, Single-Stranded Conformational Point Mutation Bestrophins Chloride Channels Macular Degeneration - genetics DNA Mutational Analysis Pedigree Alleles Adult Female Aged Genetic Variation - genetics Eye Proteins - genetics Child

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