Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by defects in phagocyte NADPH oxidase. X-linked CGD, resulting from CYBB gene mutations, accounts for approximately two-thirds of cases. Clinical manifestations typically include recurrent bacterial and fungal infections, granuloma formation, and inflammatory complications. Case presentation: We report monochorionic diamniotic twins with a novel CYBB variant (c.1303A > T, p.Lys435Ter). The 7-month-old proband presented with recurrent respiratory infections and was initially misdiagnosed with congenital cystic lung disease. His twin brother carried the identical mutation but remained asymptomatic. Neutrophil function testing demonstrated impaired respiratory burst activity. Whole-exome sequencing confirmed a de novo nonsense mutation in the CYBB gene. Conclusions: This case highlights the diagnostic challenges of CGD and illustrates remarkable phenotypic discordance in monochorionic twins with identical genetic mutations. Environmental factors and epigenetic modifications may contribute to variable expressivity. Early genetic testing is crucial for accurate diagnosis and appropriate management of suspected primary immunodeficiency disorders.

Background: X-linked severe combined immunodeficiency (X-SCID), caused by mutations in the gamma-chain gene of the interleukin-2 receptor ( IL2RG ), is a prevalent form of SCID characterized by recurrent and fatal opportunistic infections that occur early in life. Talaromyces marneffei ( T. marneffei ) infection rarely occurs in children and has a high mortality rate. Case presentation: The patient was a 7-month-old male infant who presented with recurrent cough, fever, and hepatosplenomegaly. Lymphocyte subset analysis confirmed the presence of T-B + natural killer immunodeficiency, and blood culture was positive for T. marneffei. Whole-exome sequencing revealed a novel microdeletion insertion mutation (c.818_819delins A (p. Ile273Lys fsTer21) in IL2RG , resulting in a rare shift in the amino acid sequence of the coding protein. The child was diagnosed with X-SCID due to a novel IL2RG mutation, which was further complicated by T. marneffei infection. Despite receiving systemic anti-infection treatment, the patient died 3 days after discharge. To the best of our knowledge, this novel IL2RG mutation has not been reported previously. Conclusions: For early-onset T. marneffei infection, clinicians must maintain a high index of suspicion for underlying inborn errors of immunity, and definitive diagnosis hinges on genetic testing.