Clinical characterization and identification of rare genetic variants in atypical hemolytic uremic syndrome: A Swedish retrospective observational study
| Autor: | Alexander Åkesson, Myriam Martin, Anna M. Blom, Eva Zetterberg, Migle Gabrielaite, Jenny Klintman, Maria Rossing |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty 030232 urology & nephrology Disease Complement factor I 030204 cardiovascular system & hematology urologic and male genital diseases Young Adult 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Internal medicine Atypical hemolytic uremic syndrome Genotype medicine Humans Missense mutation Atypical Hemolytic Uremic Syndrome Retrospective Studies Sweden atypical hemolytic uremic syndrome CD46 business.industry complement pathway Genetic Variation Retrospective cohort study Hematology Middle Aged medicine.disease Complement system Nephrology renal dialysis thrombotic microangiopathies Female mutation business alternative |
| Zdroj: | Åkesson, A, Martin, M, Blom, A M, Rossing, M, Gabrielaite, M, Zetterberg, E & Klintman, J 2021, ' Clinical characterization and identification of rare genetic variants in atypical hemolytic uremic syndrome : A Swedish retrospective observational study ', Therapeutic Apheresis and Dialysis, vol. 25, no. 6, pp. 988-1000 . https://doi.org/10.1111/1744-9987.13634 |
| ISSN: | 1744-9987 1744-9979 |
| DOI: | 10.1111/1744-9987.13634 |
| Popis: | INTRODUCTION: Complement-mediated atypical hemolytic uremic syndrome (aHUS) is an ultra-rare renal disease primarily caused by genetic alterations in complement proteins. The genetic work-up required for confirmation of diagnosis is complicated and not always logistically accessible. The aim of the present study was to apply a diagnostic scheme compliant with the ACMG guidelines to investigate the prevalence of complement-mediated aHUS among subjects formerly included in a retrospective cohort of clinically suspected aHUS. Clinical outcomes and genetic correlations to complement analyses were assessed.METHODS: Subjects were investigated with medical record reviewing, inquiries and laboratory analyses composed of whole genome sequencing; ELISA for factor I, factor H and factor H-specific antibodies; nephelometry for complement components 3/4; flow cytometry for CD46 surface expression and immunoblotting for the presence of factor H-related protein 1.RESULTS: In total, 45% (n=60/134) of the subjects were deceased at the time of study. Twenty of the eligible subjects consented to study participation. Based on genetic sequencing and clinical characteristics, six were categorized as definite/highly suspected complement-mediated aHUS, ten as non-complement-mediated aHUS and four as having an HUS-like phenotype. In the complement-mediated aHUS group, two subjects had not received an aHUS diagnosis during the routine clinical management. Disease-contributing/likely disease-contributing genetic variants were identified in five subjects, including a novel missense variant in the complement factor H gene (c.3450A>G,p.I1150M).CONCLUSION: The study illustrates the risk for misdiagnosis in the management of patients with complement-mediated aHUS and the importance of a comprehensive assessment of both phenotype and genotype to reach a diagnosis. This article is protected by copyright. All rights reserved. (Less) |
| Databáze: | OpenAIRE |
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