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. 2023 Sep 7:14:1254759.
doi: 10.3389/fimmu.2023.1254759. eCollection 2023.

Genetic investigation of Nordic patients with complement-mediated kidney diseases

Viktor Rydberg  1 , Sigridur Sunna Aradottir  1 , Ann-Charlotte Kristoffersson  1 , Naila Svitacheva  1 , Diana Karpman  1
Affiliations

Genetic investigation of Nordic patients with complement-mediated kidney diseases

Viktor Rydberg et al. Front Immunol. .

Erratum in

Abstract

Background: Complement activation in atypical hemolytic uremic syndrome (aHUS), C3 glomerulonephropathy (C3G) and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) may be associated with rare genetic variants. Here we describe gene variants in the Swedish and Norwegian populations.

Methods: Patients with these diagnoses (N=141) were referred for genetic screening. Sanger or next-generation sequencing were performed to identify genetic variants in 16 genes associated with these conditions. Nonsynonymous genetic variants are described when they have a minor allele frequency of <1% or were previously reported as being disease-associated.

Results: In patients with aHUS (n=94, one also had IC-MPGN) 68 different genetic variants or deletions were identified in 60 patients, of which 18 were novel. Thirty-two patients had more than one genetic variant. In patients with C3G (n=40) 29 genetic variants, deletions or duplications were identified in 15 patients, of which 9 were novel. Eight patients had more than one variant. In patients with IC-MPGN (n=7) five genetic variants were identified in five patients. Factor H variants were the most frequent in aHUS and C3 variants in C3G. Seventeen variants occurred in more than one condition.

Conclusion: Genetic screening of patients with aHUS, C3G and IC-MPGN is of paramount importance for diagnostics and treatment. In this study, we describe genetic assessment of Nordic patients in which 26 novel variants were found.

Keywords: C3 glomerulopathy; atypical hemolytic uremic syndrome; complement; genes; membranoproliferative glomerulonephritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Presentation of all genetic variants found in this study. The location of variants in the genes studied herein is presented. Variants shown above the gene domains were found in aHUS patients. Variants presented under gene domains were found in C3G cases. Variants labeled in black were previously known. Variants labelled in green are novel. Variants in bold were present in both aHUS and C3G patients. Variants in grey italics have a minor allele frequency > 1% but have been associated with complement-mediated kidney diseases. MG1-8: Macroglobulin domain 1-8. ANA: Anaphylatoxin. CUB, C1r/C1s, Urchin embryonic growth factor, Bone morphogenetic protein 1; LNK, Linker; aNT, alpha N-terminal; TED, Thiol ester-containing domain; C345C, C345C/NTR domain; FIMAC, Factor I membrane attack complex; SRCR, Scavenger receptor cysteine-rich; LDR, LDL receptor class A2; VWA, Von Willebrand factor type A; TM, Transmembrane; ST, Ser/Thr-rich; CT, Cytoplasmic domain; EGF 1-6, Epidermal growth factor-like 1-6; PAN, Plasminogen-Apple-Nematode; DAGKc, Diacylglycerol kinase catalytic domain; DAGKa, Diacylglycerol kinase accessory domain; Int, Intron; TSP t1, Thrombospondin type-1 1-5.
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