Sequence analysis of BIRC4/XIAP in male patients with common variable immunodeficiency.
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 hypogammaglobulinemic patients. We therefore estimate that XLP caused by XIAP deficiency may be a very rare differential diagnosis in male patients with CVID.
Salzer
Ulrich
U
Division of Rheumatology and Clinical Immunology, Medical School, University Hospital Freiburg, Freiburg, Germany.
Hagena
Tina
T
Webster
David B
DB
Grimbacher
Bodo
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
D007074:Immunoglobulin G; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human