A functional variant in the CFI gene confers a high risk of age-related macular degeneration

Complement factor H R1210C among Japanese patients with age-related macular degeneration

“…b Although 1 treatment using intravitreal bevacizumab and 2 treatments using focal photocoagulation stabilized the disease activity, her visual acuity remained 1/50 OD. At her final visit (6 years and 9 months after the first visit), dilated funduscopic examination revealed several drusen in the left eye and diffuse RPE damage and a massive fibrotic scar in the right eye genome sequencing using next-generation sequencers have been performed for more than 2000 Caucasian individuals with AMD, and have identified several rare AMD-susceptibility variants within known AMD-susceptibility genes [15][16][17][18][19], such sequencing has not been performed for Asian populations. Considering the ethnicity-specific nature of rare variants, high-throughput sequencing should also be applied to Asian patients with AMD; this, with the previous research on Caucasian patients, will help to clarify the mechanisms of AMD and its variable phenotypes ( Table 2).…”

“…In contrast with common SNP, rare susceptibility variants tend to have larger effects, because they sometimes result in loss of function. Studies using next-generation sequencing have revealed that rare variants located within CFH, C3, CFI, and C9 confer a high risk of AMD [15][16][17][18][19]; in particular, CFH R1210C has a large effect (odds ratio 18.8), and both relatively early-onset and drusen-rich AMD have been reported for individuals with this mutation [19]. This mutation is also known to be responsible for atypical hemolytic uremic syndrome (aHUS) [20] and primary glomerulonephritis [21].…”

Clinical Characteristics of Familial and Sporadic Age-Related Macular Degeneration: Differences and Similarities

“…Sobrin et al 15 showed that siblings are more likely to develop the same advanced subtype as their proband. This may suggest the contribution of genetic variants in these familial patients, 16,35,41 which may increase the risk for developing GA rather than CNV. Affected members of densely affected families have been reported to bear a lower SNP load than expected based on five common known AMD risk variants; CFH (rs1061170 and rs1410996), ARMS2 (rs10490924), C2-CFB (rs641153 and rs9332739).…”

“…35,41 In addition, rare highly penetrant variants in the CFI gene have been identified in patients with cuticular drusen. 16,44 Therefore, the higher prevalence of cuticular drusen in families may be explained by segregation of rare, highly penetrant variants within these families.…”

“…12 Several recent studies have shown that rare, highly penetrant genetic variants can strongly increase the risk of developing AMD in families with AMD, as well as in the AMD population in general. [16][17][18][19][20] Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: Little is known about clinical differences and similarities between patients with and without a family history for AMD. The purpose of this study is to gain more insight into the clinical and phenotypic characteristics of familial and sporadic AMD patients, and to analyze if there are distinct clinical differences between these subgroups.…”