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  Three novel mutations of the CIITA gene in MHC class II-deficient patients with a severe immunodeficiency

Dziembowska, M., Fondaneche, M.-C., Vedrenne, J., Barbieri, G., Wiszniewski, W., Picard, C., et al. (2002). Three novel mutations of the CIITA gene in MHC class II-deficient patients with a severe immunodeficiency. Immunogenetics, 53(10-11), 821-829.

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 Creators:
Dziembowska, Magda, Author
Fondaneche, Marie-Claude, Author
Vedrenne, Jocelyn, Author
Barbieri, Giovanna, Author
Wiszniewski, Wojciech, Author
Picard, Capucine, Author
Cant, Andrew J., Author
Steimle, Viktor1, Author              
Charron, Dominique, Author
Alca-Loridan, Catherine, Author
Fischer, Alain, Author
Lisowska-Grospierre, Barbara, Author
Affiliations:
1Spemann Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243655              

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Free keywords: MHC class II deficiency; MHC class II transactivator; CIITA; gene regulation; HLA
 Abstract: Four transacting genes, CHTA, RFXANK, RFX5, and RFXAP, control coordinate MHC II expression. In humans, defects in these genes result in the absence of MHC II expression and thus a combined immunodeficency. CIITA is considered to be a master MHC II regulator and is responsible for the defect in complementation group A. Eight such affected families have been reported. We investigated the molecular basis of the defect in three patients in these families, all presenting a severe immunodeficiency. CIITA transcripts were detected in all three patients but in one at an abnormally low level. Three novel heterozygous mutations of CIITA were found in patients SP and RC. One SP CIITA allele contained a nonsense mutation, G2178A, leading to a premature stop codon and the other allele in SP was found not to be expressed, In patient RC, two in-frame deletions were detected: one of the nucleotides 3003-3084 corresponding to the exon coding from Leu964 to Asp991, in the paternal allele, and a CATdel3193-5 of the isoleucine codon at position 1027, in the maternal allele. Transfection of a CIITA-deficient cell line with the recombinant CATdel3193-5-CIITA cDNA revealed a loss of function for this mutant and retention of the protein in the cytoplasm. No mutations were detected in the 4.5-kb cDNA from patient OK but the level of CIITA transcript was found to be profoundly decreased. However, promoters III and IV were not affected. This last case represents the first described CIITA dysfunction due to putative mutation(s) in cis regulatory sequences of CIITA.

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Language(s): eng - English
 Dates: 2002-01-29
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 20898
ISI: 000174662900002
 Degree: -

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Title: Immunogenetics
Source Genre: Journal
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Pages: - Volume / Issue: 53 (10-11) Sequence Number: - Start / End Page: 821 - 829 Identifier: ISSN: 0093-7711