X-Linked Agammagobulinemia in a Large Series of North African Patients: Frequency, Clinical Features and Novel BTK Mutations

Zahra Aadam 1, 2 Nadia Kechout 3 Abdelhamid Barakat 1 Koon-Wing Chan 4 Meriem Ben-Ali 5 Imen Ben-Mustapha 5 Fethi Zidi 6 Fatima Ailal 7 Nabila Attal 3 Fatouma Doudou 3 Mohamed-Cherif Abbadi 3 Chawki Kaddache 8 Leila Smati 9 Jalel Chemli 10 Nabila Touri 8 Tahar Gargah 11 Ines Brini 12 Amina Bakhchane 1 Hicham Charoute 1 Leïla Jeddane 7 Mohamed-Ridha Barbouche 5 Sara El Atiqi 7 Naima El Hafidi 13 Mustapha Hida 14 Rachid Saile 2 Hanane Salih Alj 2 Rachida Boukari 15 Mohamed Bejaoui 16 Jilali Najib 7 Yu-Lung Lau 4 Fethi Mellouli 16 Ahmed Aziz Bousfiha 7
1 Institut Pasteur du Maroc
2 Laboratory of Biology and Health URAC34—Metabolic and Immunologic pathology Research Team
3 Institut Pasteur d'Algérie
4 Department of Paediatrics and Adolescent Medicine [HKU]
5 Institut Pasteur de Tunis
6 Department of Pediatrics
7 Clinical Immunology Unit
8 Department of Pediatrics
9 Department of Pediatrics EPH Bologhine
10 Department of Pediatrics
11 Department of Pediatrics
12 Department of Pediatrics B
13 Department of Pediatric Infectious Diseases
14 Department of Pediatrics
15 Department of Pediatrics CHU Mustapaha Bacha
16 National Bone Marrow Transplantation CenterTunis
Abstract : X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton's tyrosine kinase (BTK) gene defect. XLA patients have absent or reduced number of peripheral B cells and a profound deficiency in all immunoglobulin isotypes. This multicenter study reports the clinical, immunological and molecular features of Bruton's disease in 40 North African male patients. Fifty male out of 63 (male and female) patients diagnosed with serum agammaglobulinemia and non detectable to less than 2 % peripheral B cells were enrolled. The search for BTK gene mutations was performed for all of them by genomic DNA amplification and Sanger sequencing. We identified 33 different mutations in the BTK gene in 40 patients including 12 missense mutations, 6 nonsense mutations, 6 splice-site mutations, 5 frameshift, 2 large deletions, one complex mutation and one in-frame deletion. Seventeen of these mutations are novel. This large series shows a lower frequency of XLA among male patients from North Africa with agammaglobulinemia and absent to low B cells compared with other international studies (63.5 % vs 85 %). No strong evidence for genotype-phenotype correlation was observed. This study adds to other reports from highly consanguineous North African populations, showing lower frequency of X-linked forms as compared to AR forms of the same primary immunodeficiency. Furthermore, a large number of novel BTK mutations were identified and could further help identify carriers for genetic counseling.
Keywords : novel mutations north african population XLA BTK
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Journal articles
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Submitted on : Wednesday, December 28, 2016 - 11:06:22 AM
Last modification on : Monday, October 8, 2018 - 5:44:08 PM

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Zahra Aadam, Nadia Kechout, Abdelhamid Barakat, Koon-Wing Chan, Meriem Ben-Ali, et al.. X-Linked Agammagobulinemia in a Large Series of North African Patients: Frequency, Clinical Features and Novel BTK Mutations. Journal of Clinical Immunology, Springer Verlag, 2016, 36 (3), pp.187-194. ⟨10.1007/s10875-016-0251-z⟩. ⟨pasteur-01374987⟩

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