VAV1 HAPLOINSUFFICIENCY IN COMMON VARIABLE IMMUNODEFICIENCY WITH DEFECTIVE T CELL FUNCTION

Introduction: Common variable immunodeficiency (CVID) is a primary immune disorder characterized by impaired antibody production, which is in many instances secondary to defective T cell function (TCVID). Objectives: We have previously identified a subset of T-CVID patients characterized by defective expression of Vav1, a guanine nucleotide exchanger which couples the T-cell antigen receptor to reorganization of the actin cytoskeleton. Aims: Here we have addressed the possibility that an intrinsic defect in the Vav1 gene might underlie the reduction in Vav protein observed in T cells from these patients. Methods: We report the identification in one T-CVID patient of a heterozygous deletion in Vav1. Results: The gene deletion, spanning exons 2-27, accounts for the reduction in Vav1 mRNA and protein in T cells from this patient. The disease related pedigree of this patient suggests a de novo origin of the Vav1 deletion. Conclusions: The findings highlights Vav1 as an autosomal dominant disease gene associated with CVID with defective T-cell function.