Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
Front Immunol. 2023 Sep 7;14:1254759. doi: 10.3389/fimmu.2023.1254759. eCollection 2023.
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.
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.
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.
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.
补体在非典型溶血性尿毒症综合征 (aHUS)、C3 肾小球肾炎 (C3G) 和免疫复合物介导的膜增生性肾小球肾炎 (IC-MPGN) 中的激活可能与罕见的遗传变异有关。在此，我们描述了瑞典和挪威人群中的基因变异。
具有这些诊断的患者 (n=141) 被转介进行基因筛查。对 16 个与这些疾病相关的基因进行 Sanger 或下一代测序，以确定遗传变异。当非同义遗传变异的次要等位基因频率 <1%或之前被报道与疾病相关时，将对其进行描述。
在 aHUS 患者 (n=94，其中 1 例也患有 IC-MPGN) 中，在 60 例患者中发现了 68 种不同的遗传变异或缺失，其中 18 种是新的。32 例患者有不止一种遗传变异。在 C3G 患者 (n=40) 中，在 15 例患者中发现了 29 种遗传变异、缺失或重复，其中 9 种是新的。8 例患者有不止一种变异。在 IC-MPGN 患者 (n=7) 中，在 5 例患者中发现了 5 种遗传变异。在 aHUS 和 C3G 中，补体因子 H 变异最常见，C3 变异最常见。17 种变异出现在多种疾病中。
对 aHUS、C3G 和 IC-MPGN 患者进行基因筛查对诊断和治疗至关重要。在本研究中，我们描述了对北欧患者的基因评估，其中发现了 26 种新的变异。
