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BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Primary Immunodeficiencies
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1517347

Characterization of a WAS splice-site variant in a patient with Wiskott-Aldrich syndrome

Provisionally accepted
Elisabetta Toriello Elisabetta Toriello 1Rosa Maritato Rosa Maritato 1Antonio De Rosa Antonio De Rosa 1Maria Valeria Esposito Maria Valeria Esposito 2Carla Damiano Carla Damiano 1,3Carmen Rosano Carmen Rosano 1Emilia Cirillo Emilia Cirillo 1Antonietta Tarallo Antonietta Tarallo 1,3Cosimo Abagnale Cosimo Abagnale 1Francesca Cillo Francesca Cillo 1Roberta Romano Roberta Romano 1Laura Grilli Laura Grilli 1Marika Comegna Marika Comegna 2,4Giancarlo Blasio Giancarlo Blasio 2Giancarlo Parenti Giancarlo Parenti 1,3Enrico Maria Surace Enrico Maria Surace 1Giuseppe Castaldo Giuseppe Castaldo 2,4Claudio Pignata Claudio Pignata 1Giuliana Giardino Giuliana Giardino 1*
  • 1 Section of Paediatrics, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
  • 2 CEINGE Advanced Biotechnologies, University of Naples Federico II, Naples, Campania, Italy
  • 3 Telethon Institute of Genetics and Medicine (TIGEM), Naples, Campania, Italy
  • 4 Department of Molecular Medicine and Medical Biotechnology, School of Medicine and Surgery, University of Naples Federico II, Naples, Campania, Italy

The final, formatted version of the article will be published soon.

    Wiskott-Aldrich syndrome (WAS) (MIM #301000) is a rare X-linked primary immunodeficiency due to mutations in Wiskott-Aldrich Syndrome (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 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 nucleotides 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 (VUS). 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 PCR product, we identified a premature stop at codon 269, thus consequently no Wiskott-Aldrich Syndrome protein (WASp) was detectable in peripheral blood mononuclear cells (PBMC) 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.

    Keywords: Wiskott-Aldrich, WASP, Splice-site mutation, Next generation sequencing (NGS), Gene panel

    Received: 25 Oct 2024; Accepted: 02 Jan 2025.

    Copyright: © 2025 Toriello, Maritato, De Rosa, Esposito, Damiano, Rosano, Cirillo, Tarallo, Abagnale, Cillo, Romano, Grilli, Comegna, Blasio, Parenti, Surace, Castaldo, Pignata and Giardino. 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) or licensor 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.

    * Correspondence: Giuliana Giardino, Section of Paediatrics, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy

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