X-linked lymphoproliferative disease type 1 (XLP1) due to a “de novo” missense SH2D1A Hemizygous Mutation Leading to Predominantly Antibody Deficiency
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Purpose The SAP-SLAM receptor system plays a critical role in immune regulation, with SAP deficiency leading to apoptosis resistance in T cells and disrupting immune homeostasis, as seen in XLP-1. This disorder, characterized by uncontrolled lymphoproliferation, often presents with a variable clinical spectrum. Methods We report a case of XLP-1 with dysgammaglobulinemia in a patient initially diagnosed with pediatric-onset CVID. Through quantitative and functional analysis of the SH2D1A c.164G > A (p.Arg55Gln) variant, we confirmed its pathogenicity. Results Our findings demonstrate that this variant significantly impairs B cell differentiation and proliferation independently of T cell interactions Conclusion These results support the pathogenic nature of SH2D1A R55Q and advocate for its reclassification as a pathogenic mutation.
