X-Linked Agammagobulinemia in a Large Series of North African Patients: Frequency, Clinical Features and Novel BTK Mutations
Autor: | Hicham Charoute, Jalel Chemli, Nabila Attal, Leila Jeddane, Yu-Lung Lau, Sara El Atiqi, Rachid Saile, Ahmed Aziz Bousfiha, Chawki Kaddache, Imen Ben-Mustapha, Fethi Mellouli, Naima El Hafidi, Mohamed Bejaoui, Hanane Salih Alj, Nabila Touri, Zahra Aadam, Leila Smati, Rachida Boukari, Mustapha Hida, Fatouma Doudou, Mohamed-Cherif Abbadi, Tahar Gargah, I. Brini, Fatima Ailal, J. Najib, Amina Bakhchane, Mohamed-Ridha Barbouche, Meriem Ben-Ali, Nadia Kechout, Koon-Wing Chan, Fethi Zidi, Abdelhamid Barakat |
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Přispěvatelé: | Institut Pasteur du Maroc, Réseau International des Instituts Pasteur (RIIP), Université Hassan II [Casablanca] (UH2MC), Institut Pasteur d'Algérie, Department of Paediatrics and Adolescent Medicine [HKU], The University of Hong Kong (HKU), Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Department of Pediatrics [Tozeur], Regional Hospital of Tozeur, Faculté des Sciences Aïn Chock [Casablanca] (FSAC), Centre Hospitalo-Universitaire de Blida (CHU Blida), Faculté de médecine d'Alger, Université d'Alger 1 (Benyoucef Benkhedda), Hôpital Universitaire Sahloul (CHU Sahloul), Hôpital Charles Nicolle [Tunis], Hôpital d'enfants de Tunis, Avicenne University Hospital [Rabat], Centre Hospitalier Universitaire Hassan II (CHU HII), Centre National de Greffe de la Moëlle osseuse Tunis (CNGMO), This work was supported by ACIP: A-07-2011 (Actions Concertées Inter Pasteuriennes) from the International Network of Pasteur Institutes (RIIP). |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine MESH: Sequence Analysis DNA Gene Expression MESH: Genetic Diseases X-Linked/immunology Gene mutation medicine.disease_cause MESH: Protein-Tyrosine Kinases/immunology 0302 clinical medicine Gene Frequency Agammaglobulinemia hemic and lymphatic diseases MESH: Child Agammaglobulinaemia Tyrosine Kinase Immunology and Allergy Medicine Missense mutation Age of Onset Child MESH: Genetic Diseases X-Linked/complications novel mutations MESH: Genetic Association Studies MESH: Heterozygote Sanger sequencing Genetics B-Lymphocytes Mutation biology MESH: Opportunistic Infections/diagnosis MESH: Agammaglobulinemia/diagnosis Genetic Diseases X-Linked Protein-Tyrosine Kinases MESH: Agammaglobulinaemia Tyrosine Kinase MESH: Infant 3. Good health Morocco BTK Child Preschool MESH: Agammaglobulinemia/immunology symbols MESH: Opportunistic Infections/immunology [SDV.IMM]Life Sciences [q-bio]/Immunology MESH: Genetic Counseling MESH: Tunisia MESH: Algeria Adult Heterozygote XLA Tunisia north african population MESH: Age of Onset Immunology Nonsense mutation MESH: B-Lymphocytes/pathology MESH: Opportunistic Infections/genetics Genetic Counseling Opportunistic Infections MESH: B-Lymphocytes/immunology Frameshift mutation 03 medical and health sciences symbols.namesake MESH: Opportunistic Infections/complications MESH: Genetic Diseases X-Linked/genetics Humans Bruton's tyrosine kinase [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Gene Frequency Alleles Genetic Association Studies MESH: Humans business.industry MESH: Alleles MESH: Child Preschool Infant MESH: Adult Sequence Analysis DNA MESH: Agammaglobulinemia/complications medicine.disease MESH: Gene Expression MESH: Male 030104 developmental biology MESH: Protein-Tyrosine Kinases/genetics MESH: Genetic Diseases X-Linked/diagnosis Algeria MESH: Morocco Primary immunodeficiency biology.protein MESH: Mutation MESH: Agammaglobulinemia/genetics business 030215 immunology |
Zdroj: | Journal of Clinical Immunology Journal of Clinical Immunology, Springer Verlag, 2016, 36 (3), pp.187-194. ⟨10.1007/s10875-016-0251-z⟩ |
ISSN: | 0271-9142 1573-2592 |
DOI: | 10.1007/s10875-016-0251-z⟩ |
Popis: | International audience; 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. |
Databáze: | OpenAIRE |
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