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

Allelic variation in the VMD2 gene in best disease and age-related macular degeneration
Allelic variation in the VMD2 gene in best disease and age-related macular degeneration
PURPOSE: To assess the allelic variation of the VMD2 gene in patients with Best disease and age-related macular degeneration (AMD).

METHODS: 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.

RESULTS: 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%).

CONCLUSIONS: 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.
0146-0404
1291-1296
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Munier, Francis L.
76e1c861-34a2-4da1-a28e-86cd55042760
Fishman, Gerald A.
5d293c00-72e2-41eb-b321-81149756ec6a
Weleber, Richard G.
662a5221-fd3c-4de3-b52d-53b72fce2105
Jacobson, Samuel G.
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Affatigato, Louisa M.
dcb740c4-f0a1-41ab-ab3f-30d0fe76bc20
Nichols, Brian E.
dfe2c583-3448-4f48-bf06-6c5e5e40c492
Schorderet, Daniel F.
80153f17-2467-4560-85a9-d0b41bae9226
Sheffield, Val C.
c1a1f2fe-b32b-494e-bd82-b1d90c0563fa
Stone, Edwin M.
545dc2cf-5ba2-4c9d-95aa-e22218c323c5
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Munier, Francis L.
76e1c861-34a2-4da1-a28e-86cd55042760
Fishman, Gerald A.
5d293c00-72e2-41eb-b321-81149756ec6a
Weleber, Richard G.
662a5221-fd3c-4de3-b52d-53b72fce2105
Jacobson, Samuel G.
4f5c2f74-c431-4ca1-aaa5-848e3ead0695
Affatigato, Louisa M.
dcb740c4-f0a1-41ab-ab3f-30d0fe76bc20
Nichols, Brian E.
dfe2c583-3448-4f48-bf06-6c5e5e40c492
Schorderet, Daniel F.
80153f17-2467-4560-85a9-d0b41bae9226
Sheffield, Val C.
c1a1f2fe-b32b-494e-bd82-b1d90c0563fa
Stone, Edwin M.
545dc2cf-5ba2-4c9d-95aa-e22218c323c5

Lotery, Andrew J., Munier, Francis L., Fishman, Gerald A., Weleber, Richard G., Jacobson, Samuel G., Affatigato, Louisa M., Nichols, Brian E., Schorderet, Daniel F., Sheffield, Val C. and Stone, Edwin M. (2000) Allelic variation in the VMD2 gene in best disease and age-related macular degeneration. Investigative Ophthalmology & Visual Science, 41 (6), 1291-1296. (PMID:10798642)

Record type: Article

Abstract

PURPOSE: To assess the allelic variation of the VMD2 gene in patients with Best disease and age-related macular degeneration (AMD).

METHODS: 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.

RESULTS: 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%).

CONCLUSIONS: 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.

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Published date: May 2000
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 359192
URI: https://eprints.soton.ac.uk/id/eprint/359192
ISSN: 0146-0404
PURE UUID: e8c9884e-7d45-4251-90c8-490b7ad1b036
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 01 Nov 2013 12:37
Last modified: 31 Jan 2019 01:36

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Contributors

Author: Francis L. Munier
Author: Gerald A. Fishman
Author: Richard G. Weleber
Author: Samuel G. Jacobson
Author: Louisa M. Affatigato
Author: Brian E. Nichols
Author: Daniel F. Schorderet
Author: Val C. Sheffield
Author: Edwin M. Stone

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