MAGT1 is a critical regulator of intracellular free Mg2+ in the immune system. Its loss-of-function mutations abolish the transient TCR-induced Mg2+ flux that is essential for optimal T-cell activation. Our aim is to report a case with XMEN disease.
The index patient is a 12yo boy, born at term from healthy, non-consanguineous parents, with family history of Burkitt Lymphoma in a maternal uncle. Since 5yo, he suffered recurrent cervical and abdominal lymphadenopathy. His EBV serologies showed past infection and EBV-PCR was persistently elevated. Immunological study showed dysgammaglobulinemia, normal CD4/CD8 ratio, increased TCRαβ CD4-/CD8- and low memory B cells. We analyzed NKG2D expression, intracellular signaling (Akt and S6 phosphorylation and Ikba degradation), in vitro activation assay with PMA and with specific stimuli (anti-CD3/CD28) and in vitro VEB-specific response.
Genetic analysis (NGS customized panel) revealed a novel hemizygous mutation in MAGT1 gene. The mutation, c.97_98delinsC (NM_032121), was confirmed in heterozygosity in his mother. His uncle was unaffected. NKG2D surface expression in NK and CD8+ cells was absent. Basal intracellular signaling (Akt and S6 phosphorylation) was similar than HD. Ikba degradation in B cells is normal, but there is a slight defect in CD3+ (pending on confirmation). Activation markers (CD69, CD25 and CD86) were decreased after anti-CD3/CD28 stimuli. Decreased NK degranulation upon incubation with K562 cells was observed, but it was normal after PMA/Ionomycin stimulation. VEB-specific response in vitro was impaired.
XMEN disease should be ruled out in male with impaired clearance of EBV-infection and EBV-driven lymphoproliferative complications.