title: Sequence variants of the TNFRSF13B gene in Czech CVID and IgAD patients in the context of other populations.
abstract: Mutations in the TNFRSF13B gene, encoding TACI, have been found in common variable immunodeficiency (CVID) and selective IgA deficient (IgAD) patients, but only the association with CVID seems to be significant. In this study, Czech CVID, IgAD and primary hypo/dysgammaglobulinemic (HG/DG) patients were screened for all TNFRSF13B sequence variants. The TNFRSF13B gene was mutated in 4/70 CVID patients (5.7%), 9/161 IgAD patients (5.6%), 1/17 HG/DG patient (5.9%) and none of 195 controls. Eight different mutations were detected, including the most frequent p.C104R and p.A181E mutations as well as 1 novel missense mutation, p.R189K. A significant association of TNFRSF13B gene mutations was observed in both CVID (p=0.01) and IgAD (p=0.002) Czech patients. However, when combined with all published data, only the association with CVID remained significant compared with the controls (9.9% vs. 3.2%, p<10(-6)), while statistical significance disappeared for IgAD (5.7% vs. 3.2%, p=0.145). The silent mutation p.P97P was shown to be associated significantly with CVID compared with the controls in both Czech patients (allele frequency 4.3% vs. 0.2%, p=0.01) and in connection with the published data (5.1% vs. 1.8%, p=0.003). The relevance of some TNFRSF13B gene variants remains unclear and needs to be elucidated in future studies.
authors.affiliation: Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic. tomas.freiberger@cktch.cz
authors.forename: T
authors.initials: T
authors.lastname: Freiberger
authors.forename: B
authors.initials: B
authors.lastname: Ravčuková
authors.forename: L
authors.initials: L
authors.lastname: Grodecká
authors.forename: Z
authors.initials: Z
authors.lastname: Pikulová
authors.forename: D
authors.initials: D
authors.lastname: Stikarovská
authors.forename: S
authors.initials: S
authors.lastname: Pešák
authors.forename: P
authors.initials: P
authors.lastname: Kuklínek
authors.forename: J
authors.initials: J
authors.lastname: Jarkovský
authors.forename: U
authors.initials: U
authors.lastname: Salzer
authors.forename: J
authors.initials: J
authors.lastname: Litzman
mesh_terms: D000483:Alleles; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D018153:Czech Republic; D005260:Female; D005787:Gene Frequency; D006801:Humans; D017098:IgA Deficiency / Q000235:genetics*; D007438:Introns; D008297:Male; D009154:Mutation; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein