Clinical Evaluation of 3 Families With Basal Laminar Drusen Caused by Novel Mutations in the Complement Factor H Gene

Figure 1. Sequences of heterozygous mutations detected in the CFH gene. For each CFH mutation, the chromatogram corresponding to the DNA sequence surrounding the mutation in CFH is shown. MUT indicates mutated CFH allele; WT, wild-type CFH allele.

Figure 2. Molecular genetic analyses of the CFH gene in families affected with basal laminar drusen (BLD). Squares indicate men; circles, women; slashes, deceased family members; black symbols, patients with BLD; shaded symbols, patients who display drusen but without BLD; numbers in the pedigree symbols, current age (in years); plus signs, the wild-type allele; 402H, the CFH Y402H risk allele; and 402Y, the CFH wild-type allele. Mutations are in red, risk alleles in orange, and wild-type alleles in black. A, All individuals affected by BLD were heterozygous for the p.Ile184fsX frameshift mutation with the exception of the youngest mutation carrier, who had only some soft peripheral drusen at the time of examination. B, All individuals carrying the p.Lys204fsX frameshift mutation were affected by BLD. C, Two carriers (C-II:2 and C-III:1) of the c.1697-17_-8del frameshift mutation did not display BLD.

Figure 3. Retinal phenotypes of patients carrying the CFH p.Ile184fsX frameshift mutation. Fundus photography of the right eyes showed extensive hard drusen in midperipheral retina, mostly located temporally in patient A-II:1 (A); extensive soft, hard, and crystalline drusen scattered throughout the fundus in patient A-II:3 (B); and macular hard and soft drusen in patient A-II:5 (C). The green line indicates the optical coherence tomography section. Clustered groups of hard drusen (white arrowheads) were seen in the peripheral retina of patient A-III:1 (D) and patient A-III:2 (E) by fundus photography. In patient A-III:4, fundus photography showed soft drusen in the peripheral retina (F). Fluorescein angiography of the right eye of patient A-III:1 revealed more tiny hyperfluorescent drusen (G) than the number seen on color photography (D) in the peripheral retina. Optical coherence tomography (oblique section) of patient A-II:2 showed small dome-shaped elevations of the retinal pigment epithelium (H).

Figure 4. Retinal phenotypes of patients carrying the CFH p.Lys204fsX frameshift mutation. Fundus photography of the right eyes showed extensive drusen in the posterior pole extending to the peripheral retina of patients B-II:1 (A), B-II:4 (B), and B-II:6 (C). The green line indicates the optical coherence tomography section. Fluorescein angiography of patient B-II:4 showed similar but more numerous lesions (D) compared with color photography (B). Optical coherence tomography (oblique section) showed small dome-shaped elevations of the retinal pigment epithelium (E).

Figure 5. Retinal phenotype patient C-II:4, carrier of the CFH c.1697-17_-8del splice-acceptor site mutation. Fundus photography of the right eye showed, besides the extensive drusen in the posterior pole, a subretinal hemorrhage (A), which is clearly visualized with fluorescein angiography at age 55 years (B). At age 58 years, fundus photography showed large, soft, confluent macular drusen surrounded by many hard drusen in the right eye (C). Fluorescein angiography at age 58 years showed densely packed hyperfluorescent drusen in the posterior pole of the right eye (D). Optical coherence tomography (oblique section) showed the density of the drusen by the dome-shaped elevations of the retinal pigment epithelium (E).