title: Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II deficiency.
abstract: BACKGROUND
  Major-histocompatibility-complex (MHC) class II deficiency is an autosomal recessive primary immunodeficiency disease in which MHC class II molecules are absent. It is a genetically heterogeneous disease of gene regulation resulting from defects in several transactivating genes that regulate the expression of MHC class II genes. The mutations responsible for MHC class II deficiency are classified according to complementation group (a group in which the phenotype remains uncorrected in pairwise fusions of cells). There are three known complementation groups (A, B, and C).
  
  
  METHODS
  To elucidate the genetic defect in patients with MHC class II deficiency that was not classified genetically, we performed direct complementation assays with the three genes known to regulate the expression of MHC class II genes, CIITA, RFX5, and RFXAP, and the relevant mutations were identified in each patient.
  
  
  RESULTS
  Mutations in the RFXAP gene were found in three patients from unrelated families, and the resulting defect was classified as belonging to a novel complementation group (D). Transfection with the wild-type RFXAP gene restored the expression of MHC class II molecules in the patients' cells.
  
  
  CONCLUSIONS
  Mutations in a novel MHC class II transactivating factor, RFXAP, can cause MHC class II deficiency. These mutations abolish the expression of MHC class II genes and lead to the same clinical picture of immunodeficiency as in patients with mutations in the other two MHC class II regulatory genes.
authors.affiliation: Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Villard
authors.forename: B
authors.initials: B
authors.lastname: Lisowska-Grospierre
authors.forename: P
authors.initials: P
authors.lastname: van den Elsen
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: W
authors.initials: W
authors.lastname: Reith
authors.forename: B
authors.initials: B
authors.lastname: Mach
mesh_terms: D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C093524:RFX5 protein, human; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors