Figure 1.

(A) Western blot analysis was carried out under non-reducing conditions with polyclonal anti-complement factor H-related protein 1 (FHR1). The intensity of FHR2 was much lower (around 5%) in the patient’s serum than in NHS = 100%. The positions of the two FHR2 isoform are indicated. In contrast, the intensity of complement factor H and of FHR1 appears similar in both the patient’s serum and NHS. (B) The patient’s family pedigree. The proband (filled symbol) carries two rare novel variants in the SCR1 of FHR2: a de novop.E37K missense variant (shown in red) and p.Y53* (inherited from the patient’s father). The father is a healthy carrier of p.Y53* (dotted symbol). The patient’s mother presents no variants in FHR2 (open symbol). The structure of the FHR2 protein is shown. FHR2 is composed of four SCRs. SCRs 1 and 2 (light blue) are involved in dimer formation, C3 convertase inhibition, and terminal complement component blocking. In contrast, SCRs 3 and 4 (dark blue) bind C3b and the C3d. Two FHR2 molecules form a dimer through their N-terminal SCRs. Attached carbohydrates are indicated in black.