Journal article
Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II deficiency.
- Villard J Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
- Lisowska-Grospierre B
- van den Elsen P
- Fischer A
- Reith W
- Mach B
- 1997-09-11
Published in:
- The New England journal of medicine. - 1997
Cell Line
DNA-Binding Proteins
Gene Expression Regulation
Genes, MHC Class II
Histocompatibility Antigens Class II
Humans
Immunologic Deficiency Syndromes
Mutation
Nuclear Proteins
Regulatory Factor X Transcription Factors
Trans-Activators
Transcription Factors
Transfection
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1056/NEJM199709113371104
- PMID 9287230
- Persistent URL
- https://sonar.ch/global/documents/10686
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