title: The 752delG26 mutation in the RFXANK gene associated with major histocompatibility complex class II deficiency: evidence for a founder effect in the Moroccan population.
abstract: Major histocompatibility complex class II plays a key role in the immune response, by presenting processed antigens to CD4+ lymphocytes. Major histocompatibility complex class II expression is controlled at the transcriptional level by at least four trans-acting genes: CIITA, RFXANK, RFX5 and RFXAP. Defects in these regulatory genes cause MHC class II immunodeficiency, which is frequent in North Africa. The aim of this study was to describe the immunological and molecular characteristics of ten unrelated Moroccan patients with MHC class II deficiency. Immunological examinations revealed a lack of expression of MHC class II molecules at the surface of peripheral blood mononuclear cells, low CD4+ T lymphocyte counts and variable serum immunoglobulin (IgG, IgM and IgA) levels. In addition, no MHC class II (HLA DR) expression was observed on lymphoblasts. The molecular analysis identified the same homozygous 752delG26 mutation in the RFXANK genes of all patients. This finding confirms the association between the high frequency of the combined immunodeficiency and the defect in MHC class II expression and provides strong evidence for a founder effect of the 752delG26 mutation in the North African population. These findings should facilitate the establishment of molecular diagnosis and improve genetic counselling for affected Moroccan families.
authors.affiliation: Laboratory of Immunology and Molecular Biology, Pasteur Institute, Casablanca, Morocco.
authors.forename: Hamid
authors.initials: H
authors.lastname: Naamane
authors.forename: Ouafaa
authors.initials: O
authors.lastname: El Maataoui
authors.forename: Fatima
authors.initials: F
authors.lastname: Ailal
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Barakat
authors.forename: Siham
authors.initials: S
authors.lastname: Bennani
authors.forename: Jilali
authors.initials: J
authors.lastname: Najib
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hassar
authors.forename: Rachid
authors.initials: R
authors.lastname: Saile
authors.forename: Ahmed Aziz
authors.initials: AA
authors.lastname: Bousfiha
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D004247:DNA; D004268:DNA-Binding Proteins; D005260:Female; D018703:Founder Effect; D017353:Gene Deletion; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D009018:Morocco / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D016511:Severe Combined Immunodeficiency / Q000208:ethnology* / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; C117892:RFXANK protein, human; D014157:Transcription Factors; D004247:DNA