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The 752delG26 mutation in the RFXANK gene associated with major histocompatibility complex class II deficiency: evidence for a founder effect in the Moroccan population

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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.

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Acknowledgements

We would particularly like to thank Dr Capucine Picard (Centre d’étude des déficits immunitaires. Hôpital Necker-Enfants Malades, Paris) and Professor Jean-Laurent Casanova (Rockefeller University, New York and Head of the Laboratory of Human Genetics of Infectious Diseases, INSERM-U550, Faculté Necker) for their help with the writing of this manuscript. We would also like to thank Dr EL Chadly (Cytogenetics Laboratory, Institut Pasteur du Maroc), Dr Omar Abidi (Genetics Laboratory, Institut Pasteur du Maroc) and Pr R. Barbouch (Immunology Laboratory, Institut Pasteur de la Tunisie).

The authors demonstrate to have had no financial relationship with the organisation that supported this research.

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Authors and Affiliations

  1. Laboratory of Immunology and Molecular Biology, Pasteur Institute, Casablanca, Morocco

    Hamid Naamane, Siham Bennani & Mohammed Hassar

  2. Laboratory of Immunology, Ibn Rochd University Hospital Center, Casablanca, Morocco

    Ouafaa El Maataoui

  3. Clinical Immunology Unit. Paediatric Infectious Disease Department, Ibn Rushd Hospital, Casablanca, Morocco

    Fatima Ailal, Jilali Najib & Ahmed Aziz Bousfiha

  4. Laboratory of Human Genetic, Pasteur Institute, Casablanca, Morocco

    Abdelhamid Barakat

  5. Laboratory of Research on Lipoproteins and Atherosclerosis, University of Hassan II Mohamedia, Casablanca, Morocco

    Rachid Saile

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  1. Hamid Naamane
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  2. Ouafaa El Maataoui
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  3. Fatima Ailal
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  4. Abdelhamid Barakat
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  6. Jilali Najib
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  7. Mohammed Hassar
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  8. Rachid Saile
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  9. Ahmed Aziz Bousfiha
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Correspondence to Ahmed Aziz Bousfiha.

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Naamane, H., El Maataoui, O., Ailal, F. et al. The 752delG26 mutation in the RFXANK gene associated with major histocompatibility complex class II deficiency: evidence for a founder effect in the Moroccan population. Eur J Pediatr 169, 1069–1074 (2010). https://doi.org/10.1007/s00431-010-1179-6

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  • DOI: https://doi.org/10.1007/s00431-010-1179-6

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