Two New Mutations in TACI Identified to be Causing Disease in Patients with Common Variable Immunodeficiency

Rationale: Common Variable Immunodeficiency (CVID) is a complex primary immunodeficiency with the major feature of hypogammaglobulinemia. Patients with CVID usually do not have a genetic diagnosis, however up to 15% of patients with CVID have been found to have mutations of the gene TNFRSF13Bencoding TACI (transmembrane activator and calcium-modulator and cyclophilin-ligand interacter). Six mutations have been recognized thus far that are linked to a diagnosis of CVID. Here, we identify two additional mutations that are found in the TNFRSF13B gene encoding TACI in patients with CVID.

Methods: TNFRSF13B DNA Sequencing Test was performed by LabCorp and Correlagen Diagnostics on family members of two families with CVID. The coding sequence of TNFRSF13Bwas amplified by PCR, and each PCR product then sequenced bi-directionally using the Sanger sequencing methodology.

Results: We investigated two families with CVID and identified the c.81G>A TNFRSF13B homozygous mutation in two siblings of Family A and the father and two children of Family B. There was an additional c.674a>G heterozygous mutation identified in Family A. Neither of these mutations have been previously identified to be associated with CVID, they were both labeled having as unclear significance for CVID thus the test was inconclusive.

Conclusions: We believe that in addition to the six already recognized mutations in TACI that are linked to CVID, the c.81G>A TNFRSF13B homozygous mutation and the TNFRSF13B c.674a>G heterozygous mutation are linked to CVID as well.