Identification of a novel nonsense mutation (c.1369 C > T) in the WAS gene in a neonate: a case report and literature review

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder characterized by the classic triad of microthrombocytopenia, eczema, and recurrent infections. However, neonatal onset often presents atypically, making early diagnosis challenging. We report a male neonate presenting with spontaneous petechiae, intractable thrombocytopenia, anemia, and leukopenia on the first day of life. The patient was initially misdiagnosed with immune thrombocytopenia (ITP) and showed refractoriness to conventional first-line (IVIG, corticosteroids) and second-line (recombinant human thrombopoietin) therapies. Trio-whole exome sequencing (Trio-WES) identified a novel hemizygous nonsense mutation, c.1369 C > T (p.Q457X), in exon 11 of the WAS gene. Bioinformatic analysis suggests this mutation leads to the loss of the critical C-terminal VCA domain of the WASP protein. This case expands the mutational spectrum of WAS. It highlights that for male neonates with unexplained thrombocytopenia—particularly those with reduced mean platelet volume (MPV)—early genetic testing is crucial to avoid misdiagnosis and inappropriate immunosuppressive treatment.