Uncoordinated HLA-D gene expression in a RFXANK-defective patient with MHC class II deficiency.
J Immunol
; 166(9): 5681-7, 2001 May 01.
Article
em En
| MEDLINE
| ID: mdl-11313409
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.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Antígenos HLA-D
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Regulação da Expressão Gênica
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Imunodeficiência Combinada Severa
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Genes MHC da Classe II
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article