title: Evaluation of CARMA1/CARD11 and Bob1 as candidate genes in common variable immunodeficiency.
abstract: OBJECTIVE
  The candidate gene approach has led to the detection of associations between common variable immunodeficiency (CVID) and mutations in the genes TACI, ICOS, BAFF-R, CD19, CD20, and CD81. Such mutations are present in less than 15% of cases, highlighting the complexity of the disease. Animal models for 2 genes involved in B-cell development, namely CARMA1/CARD11 and Bob1, develop an immunological phenotype similar to that seen in CVID, with low immunoglobulin serum levels, defective responses to antigen, and defective B-cell activation. The aim of this study was to evaluate CARMA1/CARD11 and Bob1 as candidate genes for the pathogenesis of CVID in a cohort of 66 patients with the disease.
  
  
  METHODS
  We performed direct gene sequencing of CARMA1/CARD11 and Bob1 in 66 patients with CVID.
  
  
  RESULTS
  Seven already reported genetic variants and 4 novel ones were found in the CARMA1/CARD11 gene, while 1 already reported variant and 1 novel variant were found in the Bob1 gene.
  
  
  CONCLUSIONS
  Although novel genetic variants were identified in both the CARMA1/CARD11 and the Bob1 gene, no disease-causing mutations were identified in our group of patients. However, 4 of the variants in CARMA1 and 1 of those in Bob1 were associated with the disease. Considering the heterogeneity and complexity of CVID, further studies are needed to better define the genetic mechanisms involved in the pathogenesis of the disease.
authors: Department of Pediatrics, Institute of Molecular Medicine "A. Nocivelli", University of Brescia, Brescia, Italy.
authors: G
authors: G
authors: Tampella
authors: M
authors: M
authors: Baronio
authors: M
authors: M
authors: Vitali
authors: A
authors: A
authors: Soresina
authors: R
authors: R
authors: Badolato
authors: S
authors: S
authors: Giliani
authors: A
authors: A
authors: Plebani
authors: V
authors: V
authors: Lougaris
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007558:Italy; D008213:Lymphocyte Activation / Q000235:genetics; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D053468:CARD Signaling Adaptor Proteins; C091546:POU2AF1 protein, human; D015534:Trans-Activators; C426242:CARD11 protein, human; D006162:Guanylate Cyclase