title: A novel compound heterozygous TACI mutation in an autosomal recessive common variable immunodeficiency (CVID) family.
abstract: Common variable immunodeficiency (CVID) is a primary immune disorder characterized by low immunoglobulin serum levels and increased susceptibility to infections. Underlying genetic causes are only known in less than 15% of patients and encompass mutations in the genes encoding for ICOS, TACI, BAFF-R, CD19, CD20, CD81 and MSH5. TACI is the most frequently mutated gene among CVID patients. We report on two pediatric Italian male siblings with hypogammaglobulinemia and recurrent respiratory and gastrointestinal infections in association with a novel compound heterozygous TACI mutation. Both patients carry the I87N/C104R mutation that has not been reported yet. This results in aberrant TACI expression and abrogates APRIL binding on EBV B cells. This study identifies a novel combined mutation in TNFRSF13B increasing the spectrum of TACI mutations associated with CVID.
authors.affiliation: Pediatrics Clinic, University of Brescia and Laboratory for Molecular Medicine A. Nocivelli, University of Brescia, Italy. vlougarisbs@yahoo.com
authors.forename: V
authors.initials: V
authors.lastname: Lougaris
authors.forename: R
authors.initials: R
authors.lastname: Gallizzi
authors.forename: M
authors.initials: M
authors.lastname: Vitali
authors.forename: M
authors.initials: M
authors.lastname: Baronio
authors.forename: A
authors.initials: A
authors.lastname: Salpietro
authors.forename: A
authors.initials: A
authors.lastname: Bergbreiter
authors.forename: U
authors.initials: U
authors.lastname: Salzer
authors.forename: R
authors.initials: R
authors.lastname: Badolato
authors.forename: A
authors.initials: A
authors.lastname: Plebani
mesh_terms: D000361:Agammaglobulinemia / Q000150:complications / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D002648:Child; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000235:genetics* / Q000276:immunology; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012141:Respiratory Tract Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics* / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism
chemical_list: C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13