Prevalence of SAP gene defects in male patients diagnosed with common variable immunodeficiency.
The molecular basis of common variable immunodeficiency (CVID) is undefined, and diagnosis requires exclusion of other diseases including X-linked lymphoproliferative disease (XLP). This rare disorder of immunedysregulation presents typically after Epstein-Barr virus infection and results from defects in the SAP (SLAM associated protein) gene. SAP mutations have been found in a few patients diagnosed previously as CVID, suggesting that XLP may mimic CVID, but no large-scale analysis of CVID patients has been undertaken. We therefore analysed 60 male CVID and hypogammaglobulinaemic patients for abnormalities in SAP protein expression and for mutations in the SAP gene. In this study only one individual, who was found later to have an X-linked family history, was found to have a genomic mutation leading to abnormal SAP cDNA and protein expression. These results demonstrate that SAP defects are rarely observed in CVID patients. We suggest that routine screening of SAP may only be necessary in patients with other suggestive clinical features.
Eastwood
D
D
Molecular Immunology Unit, Institute of Child Health, University College London, London, UK.
Gilmour
K C
KC
Nistala
K
K
Meaney
C
C
Chapel
H
H
Sherrell
Z
Z
Webster
A D
AD
Davies
E G
EG
Jones
A
A
Gaspar
H B
HB
D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D004247:DNA / Q000032:analysis*; D018076:DNA, Complementary / Q000032:analysis; D015870:Gene Expression; D016678:Genome; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D008232:Lymphoproliferative Disorders / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
D002352:Carrier Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D004247:DNA