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Chronic Granulomatous Disease in Morocco: Genetic, Immunological, and Clinical Features of 12 Patients from 10 Kindreds

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Abstract

Purpose

Chronic granulomatous disease (CGD) is characterized by an inability of phagocytes to produce reactive oxygen species (ROS), which are required to kill some microorganisms. CGD patients are known to suffer from recurrent bacterial and/or fungal infections from the first year of life onwards. From 2009 to 2013, 12 cases of CGD were diagnosed in Morocco. We describe here these Moroccan cases of CGD.

Methods

We investigated the genetic, immunological and clinical features of 12 Moroccan patients with CGD from 10 unrelated kindreds.

Results

All patients were children suffering from recurrent bacterial and/or fungal infections. All cases displayed impaired NADPH oxidase activity in nitroblue tetrazolium (NBT), dihydrorhodamine (DHR) or 2′,7′ dichlorofluorescein diacetate (DCFH-DA) assays. Mutation analysis revealed the presence of four different mutations of CYBB in four kindreds, a recurrent mutation of NCF1 in three kindreds, and a new mutation of NCF2 in three patients from a single kindred. A large deletion of CYBB gene has detected in a patient. The causal mutation in the remaining one kindred was not identified.

Conclusion

The clinical features and infectious agents found in these patients were similar to those in CGD patients from elsewhere. The results of mutation analysis differed between kindreds, revealing a high level of genetic and allelic heterogeneity among Moroccan CGD patients. The small number of patients in our cohort probably reflects a lack of awareness of physicians. Further studies on a large cohort are required to determine the incidence and prevalence of the disease, and to improve the description of the genetic and clinical features of CGD patients in Morocco.

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Acknowledgments

We would particularly like to thank the patients and their families, whose trust, support, and cooperation were essential for the collection of the data used in this study. We thank Naim Btissam, Abdellah Mouden, Khattane Rachida and Labied Driss for technical support. We also thank the Hospital Biology Center (le Centre de Biologie des Hôpitaux; CBH) in Morocco for technical support for the NBT test. We thank the members of the Laboratory of Human Genetics of Infectious Diseases in Paris for secretarial and technical assistance. We thank the Moroccan PID Society and Hajar, the Association to Help Moroccan Children with Primary Immunodeficiencies (www.hajar-maroc.org) for financial support. The Laboratory of Human Genetics of Infectious Diseases is supported by institutional grants to INSERM and The Rockefeller University, and grants from the Agence Nationale de la Recherche (ANR13-ISV3-0001-01), the March of Dimes (6-FY08-278), HOMITUB E08153KK and NEOTIM (018736). Laila Ait Baba was supported by a PhD grant from the National Center for Technical Scientific Research (CNRST) in Morocco.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Laboratory of Biology and Health URAC34—Metabolic and Immunologic pathology Research Team, Faculty of Science of Ben M’sik, King Hassan II University, Casablanca, Morocco

    Laila Ait Baba, Zahra Aadam, Rachid Saile & Hanane Salih Alj

  2. Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, King Hassan II University-Aïn Chok, Casablanca, Morocco

    Fatima Ailal, Jilali Najib & Ahmed Aziz Bousfiha

  3. Department of Pediatric, Pneumo-allergologic and Infectious Diseases, Avicennes University Hospital, Rabat, Morocco

    Naima El Hafidi & Chafiq Mahraoui

  4. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, U980, Imagine institute, Paris, France

    Marjorie Hubeau, Fabienne Jabot-Hanin, Francesca Conti, Caroline Deswarte, Laurent Abel, Jean-Laurent Casanova & Jacinta Bustamante

  5. Necker Medical School, Paris Descartes University, Paris, France

    Marjorie Hubeau, Fabienne Jabot-Hanin, Francesca Conti, Caroline Deswarte, Laurent Abel, Jean-Laurent Casanova & Jacinta Bustamante

  6. Department of Pediatrics, Al Farabi Hospital, Mohamed VI University Hospital, Oujda, Morocco

    Noufissa Benajiba

  7. Biochemistry, Immunology Laboratory, University Mohamed V agdal, Rabat, Morocco

    Leila Jeddane

  8. Laboratory of Immunology, Faculty of Sciences and Technology, King Hassan II University, Mohammedia, Morocco

    Ayoub Aglaguel

  9. Immunology Laboratory, Averroes University Hospital, University King Hassan II-Aïn Chok Casablanca, Casablanca, Morocco

    Ouafaa El Maataoui

  10. Laboratory of Genetics and Cellular Enegineering–Faculty of Medicine and Pharmacy of Casablanca, Casablanca, Morocco

    Ahmed Tissent & Norddine Habti

  11. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA

    Ruben Martinez-Barricarte, Laurent Abel & Jean-Laurent Casanova

  12. Center for the Study of Primary Immunodeficiencies, Assistance Publique–Hôpitaux de Paris AP-HP, Enfants-Malades, Paris, France

    Jacinta Bustamante

Authors
  1. Laila Ait Baba
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  2. Fatima Ailal
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  3. Naima El Hafidi
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  4. Marjorie Hubeau
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  5. Fabienne Jabot-Hanin
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  6. Noufissa Benajiba
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  7. Zahra Aadam
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  8. Francesca Conti
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  9. Caroline Deswarte
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  10. Leila Jeddane
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  11. Ayoub Aglaguel
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  12. Ouafaa El Maataoui
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  13. Ahmed Tissent
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  14. Chafiq Mahraoui
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  15. Jilali Najib
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  16. Ruben Martinez-Barricarte
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  17. Laurent Abel
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  18. Norddine Habti
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  19. Rachid Saile
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  20. Jean-Laurent Casanova
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  21. Jacinta Bustamante
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  22. Hanane Salih Alj
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  23. Ahmed Aziz Bousfiha
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Corresponding author

Correspondence to Jacinta Bustamante.

Additional information

Fatima Ailal and Naima Hafidi contributed equally to the study.

Jacinta Bustamante, Hanane Salih Alj and Ahmed Aziz Bousfiha share senior coauthorship.

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Baba, L.A., Ailal, F., El Hafidi, N. et al. Chronic Granulomatous Disease in Morocco: Genetic, Immunological, and Clinical Features of 12 Patients from 10 Kindreds. J Clin Immunol 34, 452–458 (2014). https://doi.org/10.1007/s10875-014-9997-3

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  • DOI: https://doi.org/10.1007/s10875-014-9997-3

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