| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q23.3 | Macular degeneration, early-onset | 616118 | Autosomal dominant | 3 | FBN2 | 612570 |
A number sign (#) is used with this entry because of evidence that an early-onset form of macular degeneration (EOMD) is caused by heterozygous mutation in the FBN2 gene (612570) on chromosome 5q23.
Ratnapriya et al. (2014) reported a family in which a father and 4 sons had early-onset macular dystrophy. Clinical features varied among the 5 affected individuals. The father was diagnosed with macular degeneration at 69 years of age, and examination at age 75 showed large areas of pigment epithelial atrophy in the macula of both eyes. The eldest son reported a history of distorted vision in his left eye from the age of 46 years; examination at age 52 confirmed pigmentary changes of the left macula. Another son had a history of choroidal neovascularization in the right eye at age 35. Two more sons exhibited clinical findings consistent with atrophic macular disease in their forties. There was no history of skeletal, joint, or muscle abnormalities in these patients. Examination of an unaffected daughter showed no retinal abnormalities at age 49 years, and an unaffected son reported no vision problems.
The transmission pattern of EOMD in the families reported by Ratnapriya et al. (2014) was consistent with autosomal dominant inheritance.
By whole-exome sequencing in a father and 2 sons with early-onset macular dystrophy (EOMD), Ratnapriya et al. (2014) identified heterozygosity for a missense mutation in the FBN2 gene (E1144K; 612570.0011) that was confirmed by Sanger sequencing and segregated with disease in the family. Analysis of 96 additional patients with EOMD as well as 96 patients with age-related macular degeneration (ARMD; see 603075) revealed 2 nonsynonymous rare variants, one in a maculopathy patient (M1247T; 612570.0012) and another in a patient with ARMD. Ratnapriya et al. (2014) also detected suggestive association of a common FBN2 nonsynonymous variant (V965I; rs154001) with ARMD in 10,337 cases and 11,174 controls (odds ratio, 1.10; p = 3.79 x 10(-5)). The authors concluded that rare and common variants in FBN2 contribute to both mendelian and complex forms of macular degeneration.
Ratnapriya, R., Zhan, X., Fariss, R. N., Branham, K. E., Zipprer, D., Chakarova, C. F., Sergeev, Y. V., Campos, M. M., Othman, M., Friedman, J. S., Maminishkis, A., Waseem, N. H., and 55 others. Rare and common variants in extracellular matrix gene fibrillin 2 (FBN2) are associated with macular degeneration. Hum. Molec. Genet. 23: 5827-5837, 2014. [PubMed: 24899048] [Full Text: https://doi.org/10.1093/hmg/ddu276]