title: X-Linked Agammagobulinemia in a Large Series of North African Patients: Frequency, Clinical Features and Novel BTK Mutations.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Biology and Health URAC34-Metabolic and Immunologic pathology Research Team, Faculty of Science of BenM'sik, King Hassan II University, Casablanca, Morocco.|Institut Pasteur, Human Molecular Genetic Laboratory, Casablanca, Morocco.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Aadam
authors.affiliation: Department of Immunology, Institut Pasteur d'Algérie, Faculty of Medicine, Algiers, Algeria.
authors.forename: Nadia
authors.initials: N
authors.lastname: Kechout
authors.affiliation: Institut Pasteur, Human Molecular Genetic Laboratory, Casablanca, Morocco. abdelhamid.barakat@pasteur.ma.
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Barakat
authors.affiliation: Departments of Pediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Koon-Wing
authors.initials: KW
authors.lastname: Chan
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infections (LR11IPT02), Institut Pasteur de Tunis, and University Tunis El Manar, Tunis, Tunisia.
authors.forename: Meriem
authors.initials: M
authors.lastname: Ben-Ali
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infections (LR11IPT02), Institut Pasteur de Tunis, and University Tunis El Manar, Tunis, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Ben-Mustapha
authors.affiliation: Department of Pediatrics, Regional Hospital of Tozeur, Tozeur, Tunisia.
authors.forename: Fethi
authors.initials: F
authors.lastname: Zidi
authors.affiliation: Clinical Immunology Unit, Ibn Rochd Hospital, King Hassan II University-AinChok, Casablanca, Morocco.
authors.forename: Fatima
authors.initials: F
authors.lastname: Ailal
authors.affiliation: Department of Immunology, Institut Pasteur d'Algérie, Faculty of Medicine, Algiers, Algeria.
authors.forename: Nabila
authors.initials: N
authors.lastname: Attal
authors.affiliation: Department of Immunology, Institut Pasteur d'Algérie, Faculty of Medicine, Algiers, Algeria.
authors.forename: Fatouma
authors.initials: F
authors.lastname: Doudou
authors.affiliation: Department of Immunology, Institut Pasteur d'Algérie, Faculty of Medicine, Algiers, Algeria.
authors.forename: Mohamed-Cherif
authors.initials: MC
authors.lastname: Abbadi
authors.affiliation: Department of Pediatrics, CHU Blida, Blida, Algeria.
authors.forename: Chawki
authors.initials: C
authors.lastname: Kaddache
authors.affiliation: Department of Pediatrics, EPH Bologhine, Faculty of Medicine, Algiers, Algeria.
authors.forename: Leila
authors.initials: L
authors.lastname: Smati
authors.affiliation: Department of Pediatrics, CHU Blida, Blida, Algeria.
authors.forename: Nabila
authors.initials: N
authors.lastname: Touri
authors.affiliation: Department of Pediatrics, Sahloul Hospital, Sousse, Tunisia.
authors.forename: Jalel
authors.initials: J
authors.lastname: Chemli
authors.affiliation: Department of Pediatrics, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Tahar
authors.initials: T
authors.lastname: Gargah
authors.affiliation: Department of Pediatrics B, Children's Hospital of Tunis, Tunis, Tunisia.
authors.forename: Ines
authors.initials: I
authors.lastname: Brini
authors.affiliation: Institut Pasteur, Human Molecular Genetic Laboratory, Casablanca, Morocco.
authors.forename: Amina
authors.initials: A
authors.lastname: Bakhchane
authors.affiliation: Institut Pasteur, Human Molecular Genetic Laboratory, Casablanca, Morocco.
authors.forename: Hicham
authors.initials: H
authors.lastname: Charoute
authors.affiliation: Clinical Immunology Unit, Ibn Rochd Hospital, King Hassan II University-AinChok, Casablanca, Morocco.
authors.forename: Leila
authors.initials: L
authors.lastname: Jeddane
authors.affiliation: Clinical Immunology Unit, Ibn Rochd Hospital, King Hassan II University-AinChok, Casablanca, Morocco.
authors.forename: Sara
authors.initials: S
authors.lastname: El Atiqi
authors.affiliation: Department of Pediatric Infectious Diseases, Avicenne University Hospital, Rabat, Morocco.
authors.forename: Naïma
authors.initials: N
authors.lastname: El Hafidi
authors.affiliation: Department of Pediatrics, Hassan II University Hospital, Fez, Morocco.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Hida
authors.affiliation: Laboratory of Biology and Health URAC34-Metabolic and Immunologic pathology Research Team, Faculty of Science of BenM'sik, King Hassan II University, Casablanca, Morocco.
authors.forename: Rachid
authors.initials: R
authors.lastname: Saile
authors.affiliation: Laboratory of Biology and Health URAC34-Metabolic and Immunologic pathology Research Team, Faculty of Science of BenM'sik, King Hassan II University, Casablanca, Morocco.
authors.forename: Hanane Salih
authors.initials: HS
authors.lastname: Alj
authors.affiliation: Department of Pediatrics, CHU Mustapaha Bacha, Faculty of Medicine, Algiers, Algeria.
authors.forename: Rachida
authors.initials: R
authors.lastname: Boukari
authors.affiliation: National Bone Marrow Transplantation Center, Jebel Lakhdar, Tunis, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bejaoui
authors.affiliation: Clinical Immunology Unit, Ibn Rochd Hospital, King Hassan II University-AinChok, Casablanca, Morocco.
authors.forename: Jilali
authors.initials: J
authors.lastname: Najib
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infections (LR11IPT02), Institut Pasteur de Tunis, and University Tunis El Manar, Tunis, Tunisia.
authors.forename: Mohamed-Ridha
authors.initials: MR
authors.lastname: Barbouche
authors.affiliation: Departments of Pediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: National Bone Marrow Transplantation Center, Jebel Lakhdar, Tunis, Tunisia.
authors.forename: Fethi
authors.initials: F
authors.lastname: Mellouli
authors.affiliation: Clinical Immunology Unit, Ibn Rochd Hospital, King Hassan II University-AinChok, Casablanca, Morocco.
authors.forename: Ahmed Aziz
authors.initials: AA
authors.lastname: Bousfiha
mesh_terms: D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D017668:Age of Onset; D000462:Algeria; D000483:Alleles; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D005817:Genetic Counseling; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009018:Morocco; D009154:Mutation; D009894:Opportunistic Infections / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA; D014416:Tunisia
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human
keywords: BTK; XLA; north african population; novel mutations