title: Genes associated with common variable immunodeficiency: one diagnosis to rule them all?
abstract: Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by hypogammaglobulinaemia, impaired production of specific antibodies after immunisation and increased susceptibility to infections. CVID shows a considerable phenotypical and genetic heterogeneity. In contrast to many other primary immunodeficiencies, monogenic forms count for only 2-10% of patients with CVID. Genes that have been implicated in monogenic CVID include ICOS, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), TNFRSF7 (CD27), IL21, IL21R, LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R1, VAV1, RAC2, BLK, IKZF1 (IKAROS) and IRF2BP2 With the increasing number of disease genes identified in CVID, it has become clear that CVID is an umbrella diagnosis and that many of these genetic defects cause distinct disease entities. Moreover, there is accumulating evidence that at least a subgroup of patients with CVID has a complex rather than a monogenic inheritance. This review aims to discuss current knowledge regarding the molecular genetic basis of CVID with an emphasis on the relationship with the clinical and immunological phenotype.
authors.affiliation: Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium Department of Pediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium.
authors.forename: Delfien J A
authors.initials: DJ
authors.lastname: Bogaert
authors.affiliation: Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: Melissa
authors.initials: M
authors.lastname: Dullaers
authors.affiliation: Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium Department of Internal Medicine, Ghent University, Ghent, Belgium Tumor Immunology Laboratory, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Karim Y
authors.initials: KY
authors.lastname: Vermaelen
authors.affiliation: Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Elfride
authors.initials: E
authors.lastname: De Baere
authors.affiliation: Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium Department of Pediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.
authors.forename: Filomeen
authors.initials: F
authors.lastname: Haerynck
mesh_terms: D000818:Animals; D017074:Common Variable Immunodeficiency / Q000175:diagnosis* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008967:Molecular Biology / Q000379:methods
keywords: Common Variable Immunodeficiency; Complex inheritance; Genetics; Hypogammaglobulinemia; Monogenic