Novel mutations in TNFRSF13B causing common variable immunodeficiency with paediatric presentation

ALMEJÚN MARÍA BELÉN; OLEASTRO MATÍAS; GALLICCHIO MIGUEL; ZELAZKO MARTA; DANIELIAN SILVIA

Cartagena de Indias Colombia

Congreso; First Meeting of the Latin American Society for Immunodeficiencies (LASID-2009); 2009

Latin American Society for Immunodeficiencies

Introduction: Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production. The clinical course of CVID is complicated by systemic immunopathology including gastrointestinal, lymphoproliferative, autoimmune, and granulomatous diseases. Mutations in the gene encoding TACI (Transmembrane Activator and Calcium modulator and cyclophilin ligand Interactor, TNFRSF13B) were previously found to be associated with CVID. The aim of the present study was to determine the prevalence of TNFRSF13B mutations in Argentinean patients with paediatric presentation of CVID. Material and Methods: We sequenced TNFRSF13B gene in a cohort of 32 Argentinean CVID patients with paediatric presentation of the disease. Results: From the 32 studied patients we identified 2 patients carrying a heterozygous mutation in TNFRSF13B. These mutations were not found in studying 60 control chromosomes. One of them was a previously un-described change, S231R, a missense mutation potentially affecting the cytoplasmic domain of the protein. Other novel defect was found in a patient heterozygous for the missense mutation S144L, a site affected by a reported null mutation in a CVID patient. Several additional, previously noted variants (T27T, P97P, V220A, P251L, and S277S), not associated with development of CVID, were also found in the Argentinean CVID patients at frequencies comparable to those in other Caucasian populations. The C104R mutation, previously described as the most frequent in CVID, was not found in our patients. Conclusion: TNFRSF13B mutations were observed in Argentinean CVID patients with paediatric onset of the disease in a similar frequency as in other Caucasian populations. The novel mutations identified in this study could help to further accurate the role of TACI function in the development of CVID.