Genetic investigation of Nordic patients with complement-mediated kidney diseases

Frontiers in Immunology

Immunology

Diana Karpman¹  Ann-Charlotte Kristoffersson¹  Sigridur Sunna Aradottir¹  Viktor Rydberg¹  Naila Svitacheva¹ 

[1] Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden;

关键词: complement;    atypical hemolytic uremic syndrome;    C3 glomerulopathy;    membranoproliferative glomerulonephritis;    genes;   

DOI  :  10.3389/fimmu.2023.1254759

 received in 2023-07-07, accepted in 2023-08-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundComplement 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.MethodsPatients 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.ResultsIn 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.ConclusionGenetic 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.

【 授权许可】

Unknown   
Copyright © 2023 Rydberg, Aradottir, Kristoffersson, Svitacheva and Karpman