Mutational analysis of human BLyS in patients with common variable immunodeficiency.
BLyS, a TNF family member, is crucial for B cell proliferation and differentiation by acting through its three receptors, TACI, BCMA and BAFF-R. The knock out model for BLyS is characterized by an immunological phenotype reminiscent of the human phenotype of common variable immunodeficiency (CVID). CVID is characterized by a defective B cell compartment, evidencing the putative importance of BLyS in its pathogenesis. On the contrary, the transgenic model for BLys is characterized by autoimmune manifestations, underlying its role in B cell regulation. In fact, mutations in TACI, one of the three BLyS receptors, are associated with CVID. Based on these facts, we hypothesized that BLyS could be a candidate gene for CVID. We screened 78 patients with CVID using DHPLC and direct sequencing: No disease causing mutations were identified. A novel heterozygous single nucleotide polymorphism (SNP) was found in exon 1 of one individual, however this SNP (G189A) does not lead to an amino acid substitution.
Losi
Claretta Gioia
CG
Istituto di Medicina Molecolare Angelo Nocivelli, Clinica Pediatrica, Università di Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy. gioia_losi@yahoo.it
Salzer
Ulrich
U
Gatta
Roberta
R
Lougaris
Vassilios
V
Cattaneo
Gemma
G
Meini
Antonella
A
Soresina
Annarosa
A
Grimbacher
Bodo
B
Plebani
Alessandro
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D053264:B-Cell Activating Factor; D017931:DNA Primers; D008565:Membrane Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha