ORPHA: 280598;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 14q32.12 | Macular degeneration, age-related, 3 | 608895 | Autosomal dominant | 3 | FBLN5 | 604580 |
A number sign (#) is used with this entry because of evidence that age-related macular degeneration-3 (ARMD3) is caused by heterozygous mutation in the gene encoding fibulin-5 (FBLN5; 604580) on chromosome 14q32.
Heterozygous mutation in the FBLN5 gene can also cause autosomal dominant cutis laxa-2 (ADCL2; 614434) and demyelinating Charcot-Marie-Tooth disease type 1H (CMT1H; 619764).
Age-related macular degeneration-3 (ARMD3) is characterized by numerous small round yellow lesions visible at the temporal edge of the macula. Larger, less distinct yellow areas near the center of the macula are also observed, which represent areas of pigment epithelial detachment (Stone et al., 2004).
For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration, see 603075.
Stone et al. (2004) identified 7 unrelated patients with age-related macular degeneration and mutations in the FBLN5 gene. Upon examination in a retina clinic, all 7 patients showed clusters of small, round, uniform drusen in association with variable degrees of detachment of retinal pigment epithelium. Fluorescein angiography revealed that the small dot-like lesions were brightly hyperfluorescent, whereas the areas of retinal detachment were much less visible. Three of the patients also showed evidence of choroidal neovascularization.
Mullins et al. (2007) localized the fibulin-5 protein to the Bruch membrane and to the intercapillary pillars of the choriocapillaris in normal human donor eyes. In eyes with age-related macular degeneration, they localized the protein to pathologic basal deposits beneath the retinal pigment epithelium (RPE) as well as in some small drusen. Mullins et al. (2007) suggested that fibulin-5 may promote extracellular deposit formation in macular degeneration.
Stone et al. (2004) studied 402 patients with age-related macular degeneration and identified 7 different mutations in the FBLN5 gene (604580.0003-604580.0009) that were not found in 429 controls (p = 0.006).
Mullins, R. F., Olvera, M. A., Clark, A. F., Stone, E. M. Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration. Exp. Eye Res. 84: 378-380, 2007. [PubMed: 17109857] [Full Text: https://doi.org/10.1016/j.exer.2006.09.021]
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. Missense variations in the fibulin 5 gene and age-related macular degeneration. New Eng. J. Med. 351: 346-353, 2004. [PubMed: 15269314] [Full Text: https://doi.org/10.1056/NEJMoa040833]