title: Screening of functional and positional candidate genes in families with common variable immunodeficiency.
abstract: BACKGROUND
  Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary antibody deficiencies with complex clinical and immunological phenotypes. The recent discovery that some CVID patients show monogenic defects in the genes encoding ICOS, TACI or CD19 prompted us to investigate several functional candidate genes in individuals with CVID.
  
  
  RESULTS
  The exonic, protein coding regions of the genes encoding: APRIL, BCMA, IL10, IL10Ralpha, IL10Rbeta, IL21, IL21R, and CCL18, were analyzed primarily in familial CVID cases, who showed evidence of genetic linkage to the respective candidate gene loci and CVID families with a recessive pattern of inheritance. Two novel SNPs were identified in exon 5 and exon 8 of the IL21R gene, which segregated with the disease phenotype in one CVID family. Eleven additional SNPs in the genes encoding BCMA, APRIL, IL10, IL10Ralpha, IL21 and IL21R were observed at similar frequencies as in healthy donors.
  
  
  CONCLUSIONS
  We were unable to identify obvious disease causing mutations in the protein coding regions of the analyzed genes in the studied cohort.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medical School, University Hospital Freiburg, Hugstetterstr, 55, 79106 Freiburg, Germany. salzer@medizin.ukl.uni-freiburg.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Salzer
authors.forename: Carla
authors.initials: C
authors.lastname: Neumann
authors.forename: Jens
authors.initials: J
authors.lastname: Thiel
authors.forename: Cristina
authors.initials: C
authors.lastname: Woellner
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan-Hammarström
authors.forename: Vassilis
authors.initials: V
authors.lastname: Lougaris
authors.forename: Tina
authors.initials: T
authors.lastname: Hagena
authors.forename: Johannes
authors.initials: J
authors.lastname: Jung
authors.forename: Jennifer
authors.initials: J
authors.lastname: Birmelin
authors.forename: Likun
authors.initials: L
authors.lastname: Du
authors.forename: Ayse
authors.initials: A
authors.lastname: Metin
authors.forename: David A
authors.initials: DA
authors.lastname: Webster
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Viviana
authors.initials: V
authors.lastname: Moschese
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D053301:B-Cell Maturation Antigen / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D005190:Family; D005260:Female; D005820:Genetic Testing; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053655:Receptors, Interleukin-21 / Q000235:genetics; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics; D000098546:Interleukin-21
chemical_list: D053301:B-Cell Maturation Antigen; C111792:CCL18 protein, human; D019742:Chemokines, CC; D053709:Interleukin-10 Receptor alpha Subunit; D007378:Interleukins; D053655:Receptors, Interleukin-21; C086966:TNFRSF17 protein, human; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D016753:Interleukin-10; D000098546:Interleukin-21