In 84 unrelated patients with ARMD, van de Ven et al. (2013) analyzed the candidate gene CFI (217030) and identified 2 heterozygous missense mutations: G119R (217030.0010) in 3 probands, and G188A in 1 proband and 3 affected family ... In 84 unrelated patients with ARMD, van de Ven et al. (2013) analyzed the candidate gene CFI (217030) and identified 2 heterozygous missense mutations: G119R (217030.0010) in 3 probands, and G188A in 1 proband and 3 affected family members. Neither mutation was found in 192 ancestry- and age-matched controls, and no coexisting mutations in CFH (134370) were detected in patients carrying the CFI G119R or G188A substitutions. The G188A mutation was not found in 809 unrelated ARMD cases; however, screening for the G119R variant in 1,014 ARMD cases and 711 controls revealed the variant in 11 additional cases but none of the controls, demonstrating strong association of the G119R variant with ARMD (p = 2.16 x 10(-4)). Genotyping for G119R in additional cases resulted in the variant being identified in an overall total of 20 of 3,567 cases versus only 1 of 3,937 controls, consistent with G119R conferring high risk for developing ARMD (odds ratio, 22.20; p = 3.79 x 10(-6)). Van de Ven et al. (2013) noted that most carriers of the G119R variant had stage 4 ARMD. The 1 control carrying the minor allele had numerous hard drusen in all 4 quadrants of the peripheral retina but a normal macula in both eyes. Van de Ven et al. (2013) also noted that the G119R variant had previously been reported in patients with atypical hemolytic uremia syndrome (AHUS3; 612923) (Maga et al., 2010; Fakhouri et al., 2010); however, although ARMD patients carrying the CFI G119R variant exhibited a mild subclinical decrease in renal function, there was no significant difference in renal function of ARMD patients with G119R compared to ARMD patients without G119R. Seddon et al. (2013) sequenced the exons of 681 genes within all reported ARMD loci and related pathways in 2,493 cases. First, each gene was tested for increased or decreased burden of rare variants in cases compared to controls. Seddon et al. (2013) found that 7.8% of ARMD cases compared to 2.3% of controls were carriers of rare missense CFI variants (odds ratio = 3.6; p = 2 x 10(-8)). There was a preponderance of dysfunctional variants in cases compared to controls. Seddon et al. (2013) then tested individual variants for association with disease.