دورية أكاديمية
Clinical characterization and identification of rare genetic variants in atypical hemolytic uremic syndrome: A Swedish retrospective observational study.
| العنوان: | Clinical characterization and identification of rare genetic variants in atypical hemolytic uremic syndrome: A Swedish retrospective observational study. |
|---|---|
| المؤلفون: | Åkesson A; The Clinical Coagulation Research Unit, Department of Translational Medicine, Lund University, Skane University Hospital, Malmo, Sweden., Martin M; The Medical Protein Chemistry Research Group, Department of Translational Medicine, Lund University, Malmo, Sweden., Blom AM; The Medical Protein Chemistry Research Group, Department of Translational Medicine, Lund University, Malmo, Sweden., Rossing M; Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Gabrielaite M; Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Zetterberg E; The Clinical Coagulation Research Unit, Department of Translational Medicine, Lund University, Skane University Hospital, Malmo, Sweden., Klintman J; The Clinical Coagulation Research Unit, Department of Translational Medicine, Lund University, Skane University Hospital, Malmo, Sweden. |
| المصدر: | Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy [Ther Apher Dial] 2021 Dec; Vol. 25 (6), pp. 988-1000. Date of Electronic Publication: 2021 Mar 31. |
| نوع المنشور: | Journal Article; Observational Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Pub Country of Publication: Australia NLM ID: 101181252 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-9987 (Electronic) Linking ISSN: 17449979 NLM ISO Abbreviation: Ther Apher Dial Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Carlton South, Vic., Australia : Blackwell Pub., c2003- |
| مواضيع طبية MeSH: | Atypical Hemolytic Uremic Syndrome/*genetics , Genetic Variation/*genetics, Adult ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sweden ; Young Adult |
| مستخلص: | 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 American College of Medical Genetics and Genomics 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. Subjects were investigated with medical record reviewing, inquiries, and laboratory analyses composed of whole genome sequencing; enzyme-linked immunosorbent assays for factor I, factor H, and factor H-specific antibodies; nephelometry for complement components three of four; flow cytometry for CD46 surface expression and immunoblotting for the presence of factor H-related protein 1. 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, 10 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). This 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. (© 2021 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.) |
| References: | Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Fremeaux-Bacchi V, Kavanagh D, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies conference. Kidney Int. 2017;91(3):539-51. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaime F, Dragon-Durey MA, Ngo S, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8(4):554-62. Bresin E, Rurali E, Caprioli J, Sanchez-Corral P, Fremeaux-Bacchi V, Rodriguez de Cordoba S, et al. Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol. 2013;24(3):475-86. Rodriguez de Cordoba S. aHUS: a disorder with many risk factors. Blood. 2010;115(2):158-60. Nester CM, Thomas CP. Atypical hemolytic uremic syndrome: what is it, how is it diagnosed, and how is it treated? Hematology Am Soc Hematol Educ Program. 2012;2012:617-25. Jokiranta TS. HUS and atypical HUS. Blood. 2017;129(21):2847-56. ECN Information on Routine Diagnostic Services in Europe [PDF]. http://www.ecomplement.org: European Complement Network (ECN); 2019. http://www.ecomplement.org/images/pdfs/european%20complement%20labs%20that%20provide%20routine%20diagnostic%20servcies%20v7%20july%202019.pdf. Accessed 3 Nov 2019. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24. Akesson A, Blom AM, Klintman J, Zetterberg E. Indications of underdiagnosis of atypical haemolytic uraemic syndrome in a cohort referred to the coagulation unit in Malmo, Sweden, for analysis of ADAMTS13 2007-2012. Nephrology (Carlton). 2017;22(7):555-61. Nilsson SC, Karpman D, Vaziri-Sani F, Kristoffersson AC, Salomon R, Provot F, et al. A mutation in factor I that is associated with atypical hemolytic uremic syndrome does not affect the function of factor I in complement regulation. Mol Immunol. 2007;44(8):1835-44. Foltyn Zadura A, Zipfel PF, Bokarewa MI, Sturfelt G, Jonsen A, Nilsson SC, et al. Factor H autoantibodies and deletion of complement factor H-related protein-1 in rheumatic diseases in comparison to atypical hemolytic uremic syndrome. Arthritis Res Ther. 2012;14(4):R185. Heinen S, Sanchez-Corral P, Jackson MS, Strain L, Goodship JA, Kemp EJ, et al. De novo gene conversion in the RCA gene cluster (1q32) causes mutations in complement factor H associated with atypical hemolytic uremic syndrome. Hum Mutat. 2006;27(3):292-3. Robinson JT, Thorvaldsdottir H, Wenger AM, Zehir A, Mesirov JP. Variant review with the integrative genomics viewer. Cancer Res. 2017;77(21):e31-e4. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4(7):1073-81. Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. Predicting the functional effect of amino acid substitutions and indels. PLoS One. 2012;7(10):e46688. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248-9. Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46(3):310-5. Reese MG, Eeckman FH, Kulp D, Haussler D. Improved splice site detection in genie. J Comput Biol. 1997;4(3):311-23. Jian X, Boerwinkle E, Liu X. In silico prediction of splice-altering single nucleotide variants in the human genome. Nucleic Acids Res. 2014;42(22):13534-44. Yeo G, Burge CB. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol. 2004;11(2-3):377-94. Karczewski KJ , Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581:7809:434-443. https://dx.doi.org/10.1038/s41586-020-2308-7. Bu F, Zhang Y, Wang K, Borsa NG, Jones MB, Taylor AO, et al. Genetic analysis of 400 patients refines understanding and implicates a new gene in atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2018;29(12):2809-19. Osborne AJ, Breno M, Borsa NG, Bu F, Fremeaux-Bacchi V, Gale DP, et al. Statistical validation of rare complement variants provides insights into the molecular basis of atypical hemolytic uremic syndrome and C3 Glomerulopathy. J Immunol. 2018;200(7):2464-78. Sfyroera G, Ricklin D, Reis ES, Chen H, Wu EL, Kaznessis YN, et al. Rare loss-of-function mutation in complement component C3 provides insight into molecular and pathophysiological determinants of complement activity. J Immunol. 2015;194(7):3305-16. Akesson A, Zetterberg E, Klintman J. At the cross section of thrombotic Microangiopathy and atypical hemolytic uremic syndrome: a narrative review of differential diagnostics and a Problematization of nomenclature. Ther Apher Dial. 2017;21(4):304-19. Lambre CR, Kazatchkine MD, Maillet F, Thibon M. Guinea pig erythrocytes, after their contact with influenza virus, acquire the ability to activate the human alternative complement pathway through virus-induced desialation of the cells. J Immunol. 1982;128(2):629-34. Hyvarinen S, Meri S, Jokiranta TS. Disturbed sialic acid recognition on endothelial cells and platelets in complement attack causes atypical hemolytic uremic syndrome. Blood. 2016;127(22):2701-10. Volokhina E, Westra D, Xue X, Gros P, van de Kar N, van den Heuvel L. Novel C3 mutation p.Lys65Gln in aHUS affects complement factor H binding. Pediatr Nephrol. 2012;27(9):1519-24. Nester CM, Barbour T, de Cordoba SR, Dragon-Durey MA, Fremeaux-Bacchi V, Goodship TH, et al. Atypical aHUS: state of the art. Mol Immunol. 2015;67(1):31-42. Le Clech A, Simon-Tillaux N, Provot F, Delmas Y, Vieira-Martins P, Limou S, et al. Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors. Kidney Int. 2019;95(6):1443-52. Bu F, Maga T, Meyer NC, Wang K, Thomas CP, Nester CM, et al. Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2014;25(1):55-64. Zipfel PF, Mache C, Muller D, Licht C, Wigger M, Skerka C. DEAP-HUS: deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome. Pediatr Nephrol. 2010;25(10):2009-19. |
| معلومات مُعتمدة: | Regional Funds Skane University Hospital, Region Skane; Sveriges Regering |
| فهرسة مساهمة: | Keywords: alternative; atypical hemolytic uremic syndrome; complement pathway; mutation; renal dialysis; thrombotic microangiopathies |
| تواريخ الأحداث: | Date Created: 20210220 Date Completed: 20220204 Latest Revision: 20220204 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1111/1744-9987.13634 |
| PMID: | 33609329 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1744-9987 |
|---|---|
| DOI: | 10.1111/1744-9987.13634 |