Analysis of genetic defects in patients with the common variable immunodeficiency phenotype in a single Taiwanese tertiary care hospital

Background: Seven known genetic defects, including Bruton tyrosine kinase (Btk), CD40L, and signaling lymphocyte activation molecule-associated protein (SAP) (all X-linked) and inducible costimulator molecule (ICOS), transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI), B-cell-activating factor of the tumor necrosis family receptor (BAFFR), and CD19 (all autosomal recessive), were found in patients with the phenotype of common variable immunodeficiency (CVID). Objective: To investigate these 7 candidate protein expressions and candidate gene sequences for comprehensive analysis of known genetic defects in patients with CVID. Methods: These 7 candidate protein expressions were evaluated by flow cytometry or Western blot, and candidate genes were evaluated by direct sequencing. Results: Of 9 CVID patients from a single Taiwanese tertiary care hospital, we identified 2 cousins with decreased Btk expression who had a mutated (Asp521Val) kinase domain of Btk (1694A>T in exon 15) and I patient with decreased CD40L expression who had a mutated (Thr254Met) extracellular domain of CD40L (782T>C in exon 5). Conclusion: This comprehensive approach revealed that, in Taiwan, in some patients mild forms of X-linked agammaglobulinemia and hyper-IgM syndrome caused the CVID phenotype. No mutations of SAP, ICOS, TACI, BAFFR, and CD 19 were identified in this study, although selection bias among the small study population and genetic variation may exist.