Missense Variations in the Fibulin 5 Gene and Age-Related Macular Degeneration
Open accessAbstract
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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Screening of five fibulin genes for mutations associated with AMD revealed a variant in fibulin-5 in AMD patients.
“this screeening revealed a variant in fibulin-5 in AMD patients (145).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [145]
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- Authors
- Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., & Sheffield, V. C.
- Affiliations
- University of Iowa (US)
- University of Southampton (GB)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2004-07-22
- Volume
- 351
- Issue
- 4
- Pages
- 346-353
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2062731252
- Cited by
- 324
- References
- 33
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 12 · 2020: 9 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 11 · 2015: 12 · 2014: 13 · 2013: 15 · 2012: 23
- FWCI
- 42.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- age-related macular degeneration, fibulin-5, missense mutations, genetic susceptibility, drusen, cuticular drusen, amino acid conservation, genetic polymorphism
- MeSH terms
- Aged, Calcium-Binding Proteins, Cysteine Endopeptidases, DNA Mutational Analysis, Female, Humans, Immunoglobulins, Macular Degeneration, Male, Middle Aged, Recombinant Proteins, Case-Control Studies, Extracellular Matrix Proteins, Amino Acid Substitution, Mutation, Missense, Reverse Transcriptase Polymerase Chain Reaction
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