Scientific article

Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II deficiency

Published inThe New England journal of medicine, vol. 337, no. 11, p. 748-753
Publication date1997

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.

  • Cell Line
  • DNA-Binding Proteins/ genetics/metabolism
  • Gene Expression Regulation
  • Genes, MHC Class II/ genetics
  • Histocompatibility Antigens Class II/genetics
  • Humans
  • Immunologic Deficiency Syndromes/ genetics/metabolism
  • Mutation
  • Nuclear Proteins
  • Trans-Activators/genetics
  • Transcription Factors/ genetics/metabolism
  • Transfection
Citation (ISO format)
VILLARD, Jean et al. Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II deficiency. In: The New England journal of medicine, 1997, vol. 337, n° 11, p. 748–753. doi: 10.1056/NEJM199709113371104
Main files (1)
ISSN of the journal0028-4793

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