title: Two novel mutations in the MHC class II transactivator CIITA in a second patient from MHC class II deficiency complementation group A.
abstract: Congenital MHC class II deficiency or bare lymphocyte syndrome (BLS; McKusick 209920) is caused by defects in trans-acting regulatory factors that control MHC class II expression and is therefore a disease of gene regulation. There are at least four complementation groups and the genetic and molecular dissection of this rare disease has contributed considerably to our current understanding of the molecular mechanisms governing MHC class II expression. Identification of the gene that is defective in BLS complementation group A, CIITA (MHC class II transactivator), has led to the discovery that CIITA acts as a master control factor of MHC class II expression. We have identified the CIITA mutations in a second patient from BLS group A. Two novel mutations abolish CIITA function, as shown by transfection experiments. Molecular analysis of these two novel mutations, together with the one described earlier in the first patient, is informative in terms of CIITA structure-function relationships.
authors.affiliation: Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Bontron
authors.forename: V
authors.initials: V
authors.lastname: Steimle
authors.forename: C
authors.initials: C
authors.lastname: Ucla
authors.forename: M M
authors.initials: MM
authors.lastname: Eibl
authors.forename: B
authors.initials: B
authors.lastname: Mach
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D002460:Cell Line; D002874:Chromosome Mapping; D018076:DNA, Complementary; D017353:Gene Deletion; D005802:Genes, MHC Class II; D005816:Genetic Complementation Test; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators