title: Uncoordinated HLA-D gene expression in a RFXANK-defective patient with MHC class II deficiency.
abstract: We describe the analysis of a patient, JER, presenting classical immunological features of MHC class II deficiency. Unexpectedly, some HLA transcripts (HLA-DRA, HLA-DQA, and HLA-DMA) were found to be expressed in the JER cell line at nearly wild-type levels, while HLA-DPA and the HLA-D beta-chain transcripts were not detected. Gene reporter experiments confirmed the differential transcriptional activities driven by the HLA-D promoters in the JER cells. A defect in RFXANK was first suggested by genetic complementation analyses, then assessed with the demonstration of a homozygous mutation affecting a splice donor site downstream exon 4 of RFXANK. Because the severe deletion of the resulting protein cannot account for the expression of certain HLA-D genes, minor alternative transcripts of the RFXANK gene were analyzed. We thereby showed the existence of a transcript lacking exon 4, encoding a 28-aa-deleted protein that retains a transcriptional activity. Altogether, we characterize a new type of mutation in the RFXANK gene in a MHC class II-defective patient leading to an uncoordinated expression of the HLA-D genes, and propose that this phenotype is ensured by severely limited amounts of an active, although truncated RFXANK protein.
authors: Institut National de la Santé et de la Recherche Médicale Unité 276, Institut Pasteur, Paris, France.
authors: A M
authors: AM
authors: Lennon-Duménil
authors: M R
authors: MR
authors: Barbouche
authors: J
authors: J
authors: Vedrenne
authors: T
authors: T
authors: Prod'Homme
authors: M
authors: M
authors: Béjaoui
authors: S
authors: S
authors: Ghariani
authors: D
authors: D
authors: Charron
authors: M
authors: M
authors: Fellous
authors: K
authors: K
authors: Dellagi
authors: C
authors: C
authors: Alcaïde-Loridan
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D005802:Genes, MHC Class II; D005816:Genetic Complementation Test; D006681:HLA-D Antigens / Q000096:biosynthesis / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000096:biosynthesis / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D059805:HLA-DR alpha-Chains; D006801:Humans; D007223:Infant; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D017384:Sequence Deletion; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; C117892:RFXANK protein, human; D012333:RNA, Messenger; D014157:Transcription Factors