New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohort
BackgroundWiskott-Aldrich Syndrome (WAS) is a rare and severe X-linked immunodeficiency disorder characterized by microthrombocytopenia, eczema, and increased susceptibility to infections, autoimmunity, and malignancies. This study aims to explore molecular changes in the WAS gene in Brazilian patie...
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2025-07-01
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| author | Lucas W. Santos Samuel S. Medina Jéssica O. Frade-Guanaes Lúcia H. Siqueira Luiz Gustavo R. de Lima Luiz Gustavo R. de Lima Bruna Chati Bruna Chati Marcos T. Nolasco da Silva Marcos T. Nolasco da Silva Adriana G. L. Riccetto Adriana G. L. Riccetto Paula Lyra Ana Carla A. M. Falcão Pedro P. A. Santos Regina S. W. Di Gesu Bianca Stefanello Bianca Stefanello Gabriela G. Yamaguti-Hayakawa Carmem M. S. Bonfim Maria M. S. Vilela Maria M. S. Vilela Margareth C. Ozelo Margareth C. Ozelo |
| author_facet | Lucas W. Santos Samuel S. Medina Jéssica O. Frade-Guanaes Lúcia H. Siqueira Luiz Gustavo R. de Lima Luiz Gustavo R. de Lima Bruna Chati Bruna Chati Marcos T. Nolasco da Silva Marcos T. Nolasco da Silva Adriana G. L. Riccetto Adriana G. L. Riccetto Paula Lyra Ana Carla A. M. Falcão Pedro P. A. Santos Regina S. W. Di Gesu Bianca Stefanello Bianca Stefanello Gabriela G. Yamaguti-Hayakawa Carmem M. S. Bonfim Maria M. S. Vilela Maria M. S. Vilela Margareth C. Ozelo Margareth C. Ozelo |
| author_sort | Lucas W. Santos |
| collection | DOAJ |
| description | BackgroundWiskott-Aldrich Syndrome (WAS) is a rare and severe X-linked immunodeficiency disorder characterized by microthrombocytopenia, eczema, and increased susceptibility to infections, autoimmunity, and malignancies. This study aims to explore molecular changes in the WAS gene in Brazilian patients and assess their correlation with clinical manifestations and disease severity.MethodsThirty-one patients from 27 families with thrombocytopenia suspected to have WAS or X-linked thrombocytopenia (XLT) were analyzed. Clinical evaluation, cell morphology analysis, and flow cytometry (when feasible) were performed. DNA samples underwent direct sequencing to identify WAS gene mutations.ResultsGenomic sequencing identified 17 WAS gene variants, 10 of which were novel, expanding the genetic diversity of the disorder. The most frequent WAS gene variants were primarily frameshift indels that introduced premature stop codons, with five localized in exon 10. While thrombocytopenia and small platelets were prevalent, atypical presentations, including one patient with normal platelet size, were observed. The correlation between genotype and phenotype was complex, as some patients harboring similar mutations demonstrated varying disease severities. Of the 22 confirmed cases, 12 underwent hematopoietic stem cell transplantation (HSCT), while six succumbed to severe disease complications, including opportunistic infections and malignancies.ConclusionsThe study underscores the need for early molecular diagnosis and tailored treatments, particularly HSCT, which remains the standard curative therapy. Additionally, the findings emphasize the role of genetic variation in predicting disease severity, underlining the importance of personalized medical approaches for WAS patients. |
| format | Article |
| id | doaj-art-f34c56a946ca4aa5b322e4b6a9c7fb05 |
| institution | DOAJ |
| issn | 1664-3224 |
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| publishDate | 2025-07-01 |
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| spelling | doaj-art-f34c56a946ca4aa5b322e4b6a9c7fb052025-08-20T03:09:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15855941585594New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohortLucas W. Santos0Samuel S. Medina1Jéssica O. Frade-Guanaes2Lúcia H. Siqueira3Luiz Gustavo R. de Lima4Luiz Gustavo R. de Lima5Bruna Chati6Bruna Chati7Marcos T. Nolasco da Silva8Marcos T. Nolasco da Silva9Adriana G. L. Riccetto10Adriana G. L. Riccetto11Paula Lyra12Ana Carla A. M. Falcão13Pedro P. A. Santos14Regina S. W. Di Gesu15Bianca Stefanello16Bianca Stefanello17Gabriela G. Yamaguti-Hayakawa18Carmem M. S. Bonfim19Maria M. S. Vilela20Maria M. S. Vilela21Margareth C. Ozelo22Margareth C. Ozelo23Hemocentro UNICAMP, University of Campinas, Campinas, SP, BrazilHemocentro UNICAMP, University of Campinas, Campinas, SP, BrazilHemocentro UNICAMP, University of Campinas, Campinas, SP, BrazilHemocentro UNICAMP, University of Campinas, Campinas, SP, BrazilHemocentro UNICAMP, University of Campinas, Campinas, SP, BrazilDepartment of Internal Medicine, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilHemocentro UNICAMP, University of Campinas, Campinas, SP, BrazilDepartment of Internal Medicine, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilCenter for Investigation in Pediatrics, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilDepartment of Pediatrics, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilCenter for Investigation in Pediatrics, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilDepartment of Pediatrics, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilDepartment of Pediatrics, Professor Fernando Figueira Institute of Integral Medicine (IMIP), Recife, PE, BrazilDepartment of Pediatrics, Professor Fernando Figueira Institute of Integral Medicine (IMIP), Recife, PE, BrazilDepartment of Pediatrics, Conceição Children’s Hospital (HCC), Porto Alegre, BrazilDepartment of Pediatrics, Conceição Children’s Hospital (HCC), Porto Alegre, BrazilHemocentro UNICAMP, University of Campinas, Campinas, SP, BrazilDepartment of Internal Medicine, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilHemocentro UNICAMP, University of Campinas, Campinas, SP, BrazilPediatric Blood and Marrow Transplantation Unit, Complexo Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, BrazilCenter for Investigation in Pediatrics, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilDepartment of Pediatrics, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilHemocentro UNICAMP, University of Campinas, Campinas, SP, BrazilDepartment of Internal Medicine, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, BrazilBackgroundWiskott-Aldrich Syndrome (WAS) is a rare and severe X-linked immunodeficiency disorder characterized by microthrombocytopenia, eczema, and increased susceptibility to infections, autoimmunity, and malignancies. This study aims to explore molecular changes in the WAS gene in Brazilian patients and assess their correlation with clinical manifestations and disease severity.MethodsThirty-one patients from 27 families with thrombocytopenia suspected to have WAS or X-linked thrombocytopenia (XLT) were analyzed. Clinical evaluation, cell morphology analysis, and flow cytometry (when feasible) were performed. DNA samples underwent direct sequencing to identify WAS gene mutations.ResultsGenomic sequencing identified 17 WAS gene variants, 10 of which were novel, expanding the genetic diversity of the disorder. The most frequent WAS gene variants were primarily frameshift indels that introduced premature stop codons, with five localized in exon 10. While thrombocytopenia and small platelets were prevalent, atypical presentations, including one patient with normal platelet size, were observed. The correlation between genotype and phenotype was complex, as some patients harboring similar mutations demonstrated varying disease severities. Of the 22 confirmed cases, 12 underwent hematopoietic stem cell transplantation (HSCT), while six succumbed to severe disease complications, including opportunistic infections and malignancies.ConclusionsThe study underscores the need for early molecular diagnosis and tailored treatments, particularly HSCT, which remains the standard curative therapy. Additionally, the findings emphasize the role of genetic variation in predicting disease severity, underlining the importance of personalized medical approaches for WAS patients.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1585594/fullWiskott-Aldrich syndromeWASWASp mutationthrombocytopeniainborn errors of immunity |
| spellingShingle | Lucas W. Santos Samuel S. Medina Jéssica O. Frade-Guanaes Lúcia H. Siqueira Luiz Gustavo R. de Lima Luiz Gustavo R. de Lima Bruna Chati Bruna Chati Marcos T. Nolasco da Silva Marcos T. Nolasco da Silva Adriana G. L. Riccetto Adriana G. L. Riccetto Paula Lyra Ana Carla A. M. Falcão Pedro P. A. Santos Regina S. W. Di Gesu Bianca Stefanello Bianca Stefanello Gabriela G. Yamaguti-Hayakawa Carmem M. S. Bonfim Maria M. S. Vilela Maria M. S. Vilela Margareth C. Ozelo Margareth C. Ozelo New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohort Frontiers in Immunology Wiskott-Aldrich syndrome WAS WASp mutation thrombocytopenia inborn errors of immunity |
| title | New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohort |
| title_full | New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohort |
| title_fullStr | New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohort |
| title_full_unstemmed | New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohort |
| title_short | New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohort |
| title_sort | new insights into wiskott aldrich syndrome ten novel was mutations and their clinical impact in a brazilian cohort |
| topic | Wiskott-Aldrich syndrome WAS WASp mutation thrombocytopenia inborn errors of immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1585594/full |
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