UCL Discovery

Abstract

Background: Common variable immunodeficiency (CVID) is the most common primary antibody deficiency syndrome in humans, but it remains a diagnosis of exclusion in most cases. Several genetically defined primary immunodeficiencies mimic CVID. Among them is the X-linked lymphoproliferative syndrome (XLP) which was shown to be caused by either mutations in the gene SH2D1a/SAP or, more recently, in the BIRC4/XIAP gene. Methods: We therefore analyzed a cohort of 28 male CVID patients and 2 patients with an IgG subclass deficiency for the prevalence of mutations in BIRC4, encoding for XIAP by direct sequencing. Results: All patients showed a wild-type sequence of BIRC4/XIAP. Two SNPs, rs5956583 (dbSNP126) located in exon 6 (P -> Q) and rs28382740 (dbSNP126) in the 3' untranslated region were observed at the same frequencies as reported in public databases. Conclusions: We found no patient with a defect in the coding sequence of BIRC4/XIAP in our cohort of 30 hypo-gammaglobulinemic patients. We therefore estimate that XLP caused by XIAP deficiency may be a very rare differential diagnosis in male patients with CVID. Copyright (c) 2008 S. Karger AG, Basel.