A Novel de novo IL2RG Nonsense Mutation in a Pediatric Patient with X-linked Severe Combined Immunodeficiency

Lin Wang WangAiyan Ren RenYuanyuan He HeLu Wang WangSixi Wang WangMei Tan TanYan Chen ChenPei Huang Huang^*Zuochen Du^*

• Affiliated Hospital of Zunyi Medical University, Zunyi, China

Objective: The study aims to describe the clinical manifestations, immunophenotype, and gene mutation characteristics of a child with X-linked severe combined immunodeficiency (X-SCID) caused by an IL2RG mutation (NM_000206.3; exon 2 c.216C>A, p.Cys72*), and to contextualize these findings through a review of reported cases of X-SCID associated with Talaromyces marneffei (T. marneffei) infection, highlighting the immunological and diagnostic relevance of the mutation. Results: The patient was a 4-month-old male infant presenting with chronic diarrhea, recurrent fever, and anemia, with poor response to antibiotic treatment. Laboratory tests indicated T. marneffei infection, significantly reduced T lymphocytes and NK cells, and decreased levels of immunoglobulins (IgG, IgA, IgE). Genetic testing revealed a de novo hemizygous mutation in the IL2RG gene (NM_000206.3; exon2 c.216C>A, p.Cys72*), which has not been previously reported. Flow cytometric analysis showed a severe reduction in T lymphocytes, absence of CD8 + T cells, reduced NK cells, and a normal number of B lymphocytes predominantly composed of naive cells. Six cases of IL2RG gene mutation combined with T. marneffei infection were identified in the literature, most showing fever, hepatosplenomegaly and respiratory tract infection. Conclusion: This case of X-SCID caused by a novel de novo IL2RG mutation expands the known mutation spectrum and highlights its immunological and diagnostic relevance. The review of reported cases of X-SCID with T. marneffei infection further clarifies genotype–phenotype correlations and supports improved recognition of such rare presentations.