Clinical variability of family members with the C104R mutation in transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)

J Clin Immunol. 2013 Jan;33(1):68-73. doi: 10.1007/s10875-012-9793-x. Epub 2012 Sep 15.


Purpose: Common Variable Immunodeficiency Disorder (CVID) is a complex disorder that predisposes patients to recurrent and severe infections. The C104R mutation in the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is the most frequent mutation identified in patients with CVID. We carried out a detailed immunological and molecular study in a family with a C104R mutation.

Methods: We have undertaken segregation analysis of a kindred with C104R mutations of the TACI gene. Detailed immunological and molecular investigations were carried out for this kindred and the clinical phenotype was compared to the genotype.

Results: Segregation analysis of our kindred showed that inheriting single or double copy of the C104R mutation does not consign an individual to CVID. All heterozygotes in the family were phenotypically different, ranging from asymptomatic to ill-health. A family member with a wild type TACI variant had CVID-related phenotype including IgA deficiency and type 1 diabetes. Interestingly, a family member with the homozygous C104R/C104R variant did not meet the criteria for CVID because he had excellent, albeit unsustained, vaccine responses to T cell dependent and T cell independent vaccine antigens despite profound hypogammaglobulinemia.

Conclusion: The C104R mutation does not correlate with the clinical phenotypes in this family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Child
  • Chromosome Segregation / genetics
  • Chromosome Segregation / immunology
  • Common Variable Immunodeficiency / diagnosis
  • Common Variable Immunodeficiency / genetics*
  • Common Variable Immunodeficiency / immunology*
  • Female
  • Gene Dosage / genetics
  • Gene Dosage / immunology
  • Genetic Predisposition to Disease
  • Genetic Variation / immunology*
  • Genotype
  • Humans
  • Immunophenotyping / methods
  • Male
  • Middle Aged
  • Pedigree
  • Point Mutation* / genetics
  • Point Mutation* / immunology
  • Transmembrane Activator and CAML Interactor Protein / genetics*
  • Transmembrane Activator and CAML Interactor Protein / metabolism


  • TNFRSF13B protein, human
  • Transmembrane Activator and CAML Interactor Protein