Characterization of a WAS splice-site variant in a patient with Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome (WAS) (MIM #301000) is a rare X-linked primary immunodeficiency due to mutations in the WAS gene, characterized by thrombocytopenia with small platelets, eczema, recurrent infections, and an increased incidence of autoimmunity and malignancies. A wide spectrum of mutations h...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1517347/full |
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| author | Elisabetta Toriello Rosa Maritato Antonio De Rosa Maria Valeria Esposito Carla Damiano Carla Damiano Carmen Rosano Emilia Cirillo Antonietta Tarallo Antonietta Tarallo Cosimo Abagnale Francesca Cillo Roberta Romano Laura Grilli Marika Comegna Marika Comegna Giancarlo Blasio Giancarlo Parenti Giancarlo Parenti Enrico Maria Surace Giuseppe Castaldo Giuseppe Castaldo Claudio Pignata Giuliana Giardino |
| author_facet | Elisabetta Toriello Rosa Maritato Antonio De Rosa Maria Valeria Esposito Carla Damiano Carla Damiano Carmen Rosano Emilia Cirillo Antonietta Tarallo Antonietta Tarallo Cosimo Abagnale Francesca Cillo Roberta Romano Laura Grilli Marika Comegna Marika Comegna Giancarlo Blasio Giancarlo Parenti Giancarlo Parenti Enrico Maria Surace Giuseppe Castaldo Giuseppe Castaldo Claudio Pignata Giuliana Giardino |
| author_sort | Elisabetta Toriello |
| collection | DOAJ |
| description | Wiskott-Aldrich syndrome (WAS) (MIM #301000) is a rare X-linked primary immunodeficiency due to mutations in the WAS gene, characterized by thrombocytopenia with small platelets, eczema, recurrent infections, and an increased incidence of autoimmunity and malignancies. A wide spectrum of mutations has been identified in the WAS gene responsible for a broad variety of clinical phenotypes. By using targeted next-generation sequencing (t-NGS), we identified in a 2-month-old boy with thrombocytopenia and immunological alterations a 4-nucleotide deletion from position +3 to +6 of intron 8 (c.777 + 3_777 + 6delGAGT) of WAS, currently classified on ClinVar as a variant of uncertain significance. The in-vitro characterization of the variant revealed the complete retention of intron 8 in the mature transcript, suggesting a splicing defect due to the loss of a splice donor site at the 5′-end of intron 8. By sequencing the polymerase chain reaction product, we identified a premature stop at codon 269; thus, consequently, no Wiskott-Aldrich syndrome protein (WASp) was detectable in peripheral blood mononuclear cells from the patient. Due to the total absence of a full-length WASp, it is expected that the patient will develop the severe form of the disease, although further monitoring is needed to better define his phenotype. |
| format | Article |
| id | doaj-art-c1f0b4d1c75c4b8582243f632305745b |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-c1f0b4d1c75c4b8582243f632305745b2025-01-23T06:55:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15173471517347Characterization of a WAS splice-site variant in a patient with Wiskott-Aldrich syndromeElisabetta Toriello0Rosa Maritato1Antonio De Rosa2Maria Valeria Esposito3Carla Damiano4Carla Damiano5Carmen Rosano6Emilia Cirillo7Antonietta Tarallo8Antonietta Tarallo9Cosimo Abagnale10Francesca Cillo11Roberta Romano12Laura Grilli13Marika Comegna14Marika Comegna15Giancarlo Blasio16Giancarlo Parenti17Giancarlo Parenti18Enrico Maria Surace19Giuseppe Castaldo20Giuseppe Castaldo21Claudio Pignata22Giuliana Giardino23Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyCEINGE-Biotecnologie Avanzate Franco Salvatore S.c.a.r.l., Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyCEINGE-Biotecnologie Avanzate Franco Salvatore S.c.a.r.l., Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, Federico II University of Naples, Naples, ItalyCEINGE-Biotecnologie Avanzate Franco Salvatore S.c.a.r.l., Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyCEINGE-Biotecnologie Avanzate Franco Salvatore S.c.a.r.l., Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, Federico II University of Naples, Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyDepartment of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, ItalyWiskott-Aldrich syndrome (WAS) (MIM #301000) is a rare X-linked primary immunodeficiency due to mutations in the WAS gene, characterized by thrombocytopenia with small platelets, eczema, recurrent infections, and an increased incidence of autoimmunity and malignancies. A wide spectrum of mutations has been identified in the WAS gene responsible for a broad variety of clinical phenotypes. By using targeted next-generation sequencing (t-NGS), we identified in a 2-month-old boy with thrombocytopenia and immunological alterations a 4-nucleotide deletion from position +3 to +6 of intron 8 (c.777 + 3_777 + 6delGAGT) of WAS, currently classified on ClinVar as a variant of uncertain significance. The in-vitro characterization of the variant revealed the complete retention of intron 8 in the mature transcript, suggesting a splicing defect due to the loss of a splice donor site at the 5′-end of intron 8. By sequencing the polymerase chain reaction product, we identified a premature stop at codon 269; thus, consequently, no Wiskott-Aldrich syndrome protein (WASp) was detectable in peripheral blood mononuclear cells from the patient. Due to the total absence of a full-length WASp, it is expected that the patient will develop the severe form of the disease, although further monitoring is needed to better define his phenotype.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1517347/fullWiskott-AldrichWASPsplice-site mutationnext-generation sequencing (NGS)gene panel |
| spellingShingle | Elisabetta Toriello Rosa Maritato Antonio De Rosa Maria Valeria Esposito Carla Damiano Carla Damiano Carmen Rosano Emilia Cirillo Antonietta Tarallo Antonietta Tarallo Cosimo Abagnale Francesca Cillo Roberta Romano Laura Grilli Marika Comegna Marika Comegna Giancarlo Blasio Giancarlo Parenti Giancarlo Parenti Enrico Maria Surace Giuseppe Castaldo Giuseppe Castaldo Claudio Pignata Giuliana Giardino Characterization of a WAS splice-site variant in a patient with Wiskott-Aldrich syndrome Frontiers in Immunology Wiskott-Aldrich WASP splice-site mutation next-generation sequencing (NGS) gene panel |
| title | Characterization of a WAS splice-site variant in a patient with Wiskott-Aldrich syndrome |
| title_full | Characterization of a WAS splice-site variant in a patient with Wiskott-Aldrich syndrome |
| title_fullStr | Characterization of a WAS splice-site variant in a patient with Wiskott-Aldrich syndrome |
| title_full_unstemmed | Characterization of a WAS splice-site variant in a patient with Wiskott-Aldrich syndrome |
| title_short | Characterization of a WAS splice-site variant in a patient with Wiskott-Aldrich syndrome |
| title_sort | characterization of a was splice site variant in a patient with wiskott aldrich syndrome |
| topic | Wiskott-Aldrich WASP splice-site mutation next-generation sequencing (NGS) gene panel |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1517347/full |
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