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
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