title: Mutational analysis of human BAFF receptor TNFRSF13C (BAFF-R) in patients with common variable immunodeficiency.
abstract: BAFF receptor (BAFF-R/BR3/TNFRSF13C) is a recently identified molecule that specifically binds BLyS, a protein belonging to the tumor necrosis factor (TNF) family, and is involved in survival and maturation of B cells. Recent studies have demonstrated that mice defective in BAFF-R gene exhibit an altered profile of the B cell pool, a phenotype observed in BLyS knockout mice as well. These features suggest that mutations in this gene may result in humoral immunodeficiency. To test this hypothesis, we sequenced the BAFF-R gene in 48 patients with common variable immunodeficiency (CVID) along with 57 healthy controls. We have identified three novel variants present at the heterozygous state leading to amino acid substitutions, and have also confirmed the existence of a previously reported intronic variant. The hereby described novel variants were also present in healthy controls and in the healthy patients' parents. These variants do not affect the expression of BAFF-R neither at the mRNA nor at the protein level, suggesting that these variants represent novel polymorphic variants of the BAFF-R gene.
authors.affiliation: Clinica Pediatrica and Istituto di Medicina Molecolare Angelo Nocivelli, Spedali Civili, Brescia, Italy. gioia_losi@yahoo.it
authors.forename: Claretta Gioia
authors.initials: CG
authors.lastname: Losi
authors.forename: Antonietta
authors.initials: A
authors.lastname: Silini
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorini
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.forename: Antonella
authors.initials: A
authors.lastname: Meini
authors.forename: Simona
authors.initials: S
authors.lastname: Ferrari
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D053265:B-Cell Activation Factor Receptor; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D053265:B-Cell Activation Factor Receptor; D008565:Membrane Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C435926:TNFRSF13C protein, human