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. 2021 Jun 11;12:670727. doi: 10.3389/fgene.2021.670727

FIGURE 6.

FIGURE 6

The CFHR31–5-CFHR410 hybrid gene identified in a DDD patient in cluster 3. (A) Results of MLPA showing in patient #1678 two normal copies of CFH, only one copy of CFHR3 lacking exon 6, zero copies of CFHR1, one normal and one partially deleted copy of CFHR4 and two copies of CFHR5. (B) Pedigree (#913) of the DDD patient (II-1; indicated by the black circle) carrying the CFHR31–5-CFHR410 hybrid gene on one allele and the CFHR3-CFHR1 del on the other allele. The CFHR31–5-CFHR410 hybrid gene is indicated in red (H) and the CFHR3-CFHR1 del is indicated in green (Δ). The patient also carries two heterozygous nonsense rare variants of unknown significance (VUS) in the CFHR2 (p.Gln211Ter - rs41299605 – and p.Arg254Ter – rs41313888 -; gnomAD global MAF: 6.5 × 10–5 and 7.5 × 10–4, respectively), indicated in blue (X). The CFHR31–5-CFHR410 hybrid gene, but not the CFHR2 rare variants (RVs) and the CFHR3-CFHR1 del, was transmitted to the two healthy patients’ sons (III-1 and III-2). (C) Western Blot (WB) of FHR3 was performed using an anti-FHR3 polyclonal antiserum (diluted 1:2,000), under non-reducing conditions, using the sera from the proband (II-1), her healthy son (III-2), a healthy control with normal CNVs (positive control) and a patient carrying the homozygous CFHR3-CFHR1 del (negative control). The presence of 3 bands in the proband, corresponding to the different glycosylated variants of FHR3, indicates that the FHR31–4-FHR49 hybrid protein is secreted, since she is CFHR3-CFHR1 deleted on the other allele.