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

Magda Dziembowska, Marie Claude Fondaneche, Jocelyn Vedrenne, Giovanna Barbieri, Wojciech Wiszniewski, Capucine Picard, Andrew J. Cant, Viktor Steimle, Dominique Charron, Catherine Alcaïde-Loridan, Alain Fischer, Barbara Lisowska-Grospierre

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Four transacting genes, CIITA, 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 immunodeficiency. 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 CATde13193-5 of the isoleucine codon at position 1027, in the maternal allele. Transfection of a CIITA-deficient cell line with the recombinant CATde13193-5-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.

Original languageEnglish (US)
Pages (from-to)821-829
Number of pages9
Issue number10-11
StatePublished - 2002
Externally publishedYes


  • Gene regulation
  • HLA
  • MHC class II deficiency
  • MHC class II transactivator

ASJC Scopus subject areas

  • Immunology
  • Genetics


Dive into the research topics of 'Three novel mutations of the CIITA gene in MHC class II-deficient patients with a severe immunodeficiency'. Together they form a unique fingerprint.

Cite this