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Genetic investigation of Nordic patients with complement-mediated kidney diseases

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 popul...

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Autores principales: Rydberg, Viktor, Aradottir, Sigridur Sunna, Kristoffersson, Ann-Charlotte, Svitacheva, Naila, Karpman, Diana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513385/
https://www.ncbi.nlm.nih.gov/pubmed/37744338
http://dx.doi.org/10.3389/fimmu.2023.1254759
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author Rydberg, Viktor
Aradottir, Sigridur Sunna
Kristoffersson, Ann-Charlotte
Svitacheva, Naila
Karpman, Diana
author_facet Rydberg, Viktor
Aradottir, Sigridur Sunna
Kristoffersson, Ann-Charlotte
Svitacheva, Naila
Karpman, Diana
author_sort Rydberg, Viktor
collection PubMed
description 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.
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spelling pubmed-105133852023-09-22 Genetic investigation of Nordic patients with complement-mediated kidney diseases Rydberg, Viktor Aradottir, Sigridur Sunna Kristoffersson, Ann-Charlotte Svitacheva, Naila Karpman, Diana Front Immunol Immunology 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. Frontiers Media S.A. 2023-09-07 /pmc/articles/PMC10513385/ /pubmed/37744338 http://dx.doi.org/10.3389/fimmu.2023.1254759 Text en Copyright © 2023 Rydberg, Aradottir, Kristoffersson, Svitacheva and Karpman https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Rydberg, Viktor
Aradottir, Sigridur Sunna
Kristoffersson, Ann-Charlotte
Svitacheva, Naila
Karpman, Diana
Genetic investigation of Nordic patients with complement-mediated kidney diseases
title Genetic investigation of Nordic patients with complement-mediated kidney diseases
title_full Genetic investigation of Nordic patients with complement-mediated kidney diseases
title_fullStr Genetic investigation of Nordic patients with complement-mediated kidney diseases
title_full_unstemmed Genetic investigation of Nordic patients with complement-mediated kidney diseases
title_short Genetic investigation of Nordic patients with complement-mediated kidney diseases
title_sort genetic investigation of nordic patients with complement-mediated kidney diseases
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513385/
https://www.ncbi.nlm.nih.gov/pubmed/37744338
http://dx.doi.org/10.3389/fimmu.2023.1254759
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