Genes associated with common variable immunodeficiency: one diagnosis to rule them all?

Common variable immunodeficiency (CVID) is an immune disorder characterized by low antibody levels and an increased susceptibility to infections and immune-related complications. It is a heterogeneous disorder with a variable clinical presentation and severity. Thus far, single gene defects have been identified in about 2-10% of patients. As more disease genes are being identified, it is becoming clear that CVID is an umbrella diagnosis and that many of these genetic defects cause separate disease entities. Moreover, it is thought that, in at least a subgroup of CVID patients, a single genetic defect does not suffice to develop the disease, meaning that additional genetic and/or environmental factors are involved. This review provides an overview of disease genes implicated in CVID and discusses current evidence on a possible multifactorial origin of this disorder. (Delfien Bogaert on behalf of all authors, http://jmg.bmj.com/content/early/2016/06/01/jmedgenet-2015-103690 )