title: Mutational analysis of human BLyS in patients with common variable immunodeficiency.
abstract: 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.
authors.affiliation: Istituto di Medicina Molecolare Angelo Nocivelli, Clinica Pediatrica, Università di Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy. gioia_losi@yahoo.it
authors.forename: Claretta Gioia
authors.initials: CG
authors.lastname: Losi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Salzer
authors.forename: Roberta
authors.initials: R
authors.lastname: Gatta
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.forename: Gemma
authors.initials: G
authors.lastname: Cattaneo
authors.forename: Antonella
authors.initials: A
authors.lastname: Meini
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
mesh_terms: 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*
chemical_list: D053264:B-Cell Activating Factor; D017931:DNA Primers; D008565:Membrane Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha