Missense variations in the fibulin 5 gene and age-related macular degeneration
Missense variations in the fibulin 5 gene and age-related macular degeneration
Background: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world. The study of a rare mendelian form of macular degeneration implicated fibulin genes in the pathogenesis of more common forms of this disease. We evaluated five fibulin genes in a large series of patients with AMD.
Methods: We studied 402 patients with AMD and 429 control subjects from the same clinic population. Patients were examined by means of indirect ophthalmoscopy, slit-lamp microscopy, and fundus photography to establish the presence and phenotypic pattern of AMD. DNA samples were screened for sequence variations in five members of the fibulin gene family.
Results: Amino acid-altering sequence variations were found in all five fibulin genes, many of which were observed only in patients with AMD. Several of the altered residues have been conserved during evolution. Seven of the 402 patients with AMD had amino acid-altering sequence variations in the fibulin 5 gene, whereas none were observed among 429 control subjects (P<0.01). In addition, these seven patients all had small, circular drusen, which are commonly referred to as basal laminar or cuticular drusen.
Conclusions: Missense mutations in the fibulin 5 gene were found in 1.7 percent of patients with AMD. Many variations in other fibulin genes were also found in these patients, and the evolutionary conservation of the affected residues suggests that several of these variations may also be involved in AMD.
346-353
Stone, Edwin M.
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Braun, Terry A.
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Russell, Stephen R.
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Kuehn, Markus H.
b73e01e0-2af9-432f-8e49-d3c4270df04d
Lotery, Andrew J.
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Moore, Paula A.
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Eastman, Christopher G.
85e1fffa-3a31-4790-ab22-ad08b6922d17
Casavant, Thomas L.
ed0cc4df-4b16-499d-a217-ee09f904e366
Sheffield, Val C.
c1a1f2fe-b32b-494e-bd82-b1d90c0563fa
July 2004
Stone, Edwin M.
545dc2cf-5ba2-4c9d-95aa-e22218c323c5
Braun, Terry A.
3964cac3-ddc9-40f3-8fa9-8abec30afd28
Russell, Stephen R.
f8f01d5a-13b7-4cbc-963d-8f48f4a2d6d0
Kuehn, Markus H.
b73e01e0-2af9-432f-8e49-d3c4270df04d
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Moore, Paula A.
9458b4b3-aea5-488c-ba5a-0713bf0f133d
Eastman, Christopher G.
85e1fffa-3a31-4790-ab22-ad08b6922d17
Casavant, Thomas L.
ed0cc4df-4b16-499d-a217-ee09f904e366
Sheffield, Val C.
c1a1f2fe-b32b-494e-bd82-b1d90c0563fa
Stone, Edwin M., Braun, Terry A., Russell, Stephen R., Kuehn, Markus H., Lotery, Andrew J., Moore, Paula A., Eastman, Christopher G., Casavant, Thomas L. and Sheffield, Val C.
(2004)
Missense variations in the fibulin 5 gene and age-related macular degeneration.
New England Journal of Medicine, 351 (4), .
(doi:10.1056/NEJMoa040833).
Abstract
Background: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world. The study of a rare mendelian form of macular degeneration implicated fibulin genes in the pathogenesis of more common forms of this disease. We evaluated five fibulin genes in a large series of patients with AMD.
Methods: We studied 402 patients with AMD and 429 control subjects from the same clinic population. Patients were examined by means of indirect ophthalmoscopy, slit-lamp microscopy, and fundus photography to establish the presence and phenotypic pattern of AMD. DNA samples were screened for sequence variations in five members of the fibulin gene family.
Results: Amino acid-altering sequence variations were found in all five fibulin genes, many of which were observed only in patients with AMD. Several of the altered residues have been conserved during evolution. Seven of the 402 patients with AMD had amino acid-altering sequence variations in the fibulin 5 gene, whereas none were observed among 429 control subjects (P<0.01). In addition, these seven patients all had small, circular drusen, which are commonly referred to as basal laminar or cuticular drusen.
Conclusions: Missense mutations in the fibulin 5 gene were found in 1.7 percent of patients with AMD. Many variations in other fibulin genes were also found in these patients, and the evolutionary conservation of the affected residues suggests that several of these variations may also be involved in AMD.
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Published date: July 2004
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Local EPrints ID: 24967
URI: http://eprints.soton.ac.uk/id/eprint/24967
PURE UUID: 2f444f6a-ecea-4ebd-8d91-7808e2f2a19e
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Date deposited: 06 Apr 2006
Last modified: 16 Mar 2024 03:31
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Author:
Edwin M. Stone
Author:
Terry A. Braun
Author:
Stephen R. Russell
Author:
Markus H. Kuehn
Author:
Paula A. Moore
Author:
Christopher G. Eastman
Author:
Thomas L. Casavant
Author:
Val C. Sheffield
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