title: Novel mutations in TACI (TNFRSF13B) causing common variable immunodeficiency.
abstract: BACKGROUND
  Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production. The disorder is also characterized by co-occurrence of autoimmune, lymphoproliferative, and granulomatous diseases. Mutations in the gene encoding TACI (Transmembrane Activator and CAML Interactor, TNFRSF13B) were previously found to be associated with CVID.
  
  
  METHODS
  We therefore sequenced TNFRSF13B gene in a cohort of 48 Iranian CVID patients. Expression of TACI and binding of A proliferation-inducing ligand (APRIL) were tested by FACS.
  
  
  RESULTS
  We identified one patient with a homozygous G to T substitution in the TNFRSF13B gene at the splice site of intron 1 (c.61+1G>T), which abolished expression of the TACI molecule and binding capacity of APRIL. This represents the second CVID patient in the world with a complete absence of TACI expression. B cell lines from family members carrying the same mutation in a heterozygous form showed a reduced level of TACI expression and APRIL-binding capacity, suggesting a gene dosage effect. In addition, we found the previously recognized C104R and C172Y mutations in a heterozygous form in two patients with CVID and one, novel, heterozygous P42T mutation.
  
  
  CONCLUSIONS
  TACI mutations were observed in Iran CVID patients in a similar frequency as in other Caucasian populations. The novel mutations identified in this study support the notion of a crucial role for TACI in B cell differentiation.
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Javad
authors.initials: J
authors.lastname: Mohammadi
authors.forename: Chonghai
authors.initials: C
authors.lastname: Liu
authors.forename: Asghar
authors.initials: A
authors.lastname: Aghamohammadi
authors.forename: Astrid
authors.initials: A
authors.lastname: Bergbreiter
authors.forename: Likun
authors.initials: L
authors.lastname: Du
authors.forename: Jiayi
authors.initials: J
authors.lastname: Lu
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Amirzargar
authors.forename: Mostafa
authors.initials: M
authors.lastname: Moin
authors.forename: Ulrich
authors.initials: U
authors.lastname: Salzer
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan-Hammarström
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D015331:Cohort Studies; D017074:Common Variable Immunodeficiency / Q000209:etiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D018628:Gene Dosage; D006720:Homozygote; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D009154:Mutation; D010375:Pedigree; D011485:Protein Binding; D053303:Transmembrane Activator and CAML Interactor Protein / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; 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