Identification of the gene responsible for an autosomal dominant form of Common Variable Immunodeficiency

Common Variable Immunodeficiency (CVID) represents the most common symptomatic immunodeficiency in Europe. It is characterized by the inability to produce antibodies. Patients have an increase susceptibility to infections, mainly of the respiratory tract, with permanent lung damage, respiratory failure and eventually death even at young age. Mutations in several genes have been identified in about 20% of cases, but the genetic defect responsible for the disease in the majority of CVID patients remains unknown. The clinical spectrum of CVID disease is extremely variable: some patients are affected by severe clinical manifestations such as autoimmunity, lymphoproliferative disorders that sometime progress to lymphoma, and malignancies with a high susceptibility to gastric cancer. It is very important to recognize the genetic and biological mechanisms underlying such heterogeneity, in order to address the appropriate therapeutical approach in each patient. In this project, we will focus on the identification of a new gene responsible for CVID in a large family with an autosomal dominant inheritance of the disease, using an innovative sequencing technology, the so called "Next Generation Sequencing".