title: Cohort of Iranian Patients with Congenital Agammaglobulinemia: Mutation Analysis and Novel Gene Defects.
abstract: OBJECTIVE
  Impairment in early B-cell development can cause a predominantly antibody deficiency with severe depletion of peripheral B-cells. Mutations in the gene encoding for Bruton's-tyrosine-kinase (BTK) and the components of the pre-B-cell receptor complex or downstream signaling molecules have been related to this defect in patients with agammaglobulinemia.
  
  
  METHODS
  Iranian patients with congenital agammaglobulinemia were included and the correlation between disease-causing mutations and parameters such as clinical and immunologic phenotypes were evaluated in available patients.
  
  
  RESULTS
  Out of 87 patients, a molecular investigation was performed on 51 patients leading to identification of 39 cases with BTK (1 novel mutation), 5 cases of µ-heavy chain (3 novel mutations) and 1 case of Igα-deficiencies.
  
  
  CONCLUSIONS
  Although there is no comprehensive correlation between type of responsible BTK mutation and severity of clinical phenotype, our data suggest that BTK-deficient and autosomal recessive agammaglobulinemia patients differ significantly regarding clinical/immunologic characteristics.
authors.affiliation: a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.|b Division of Clinical Immunology, Department of Laboratory Medicine , Karolinska Institutet at Karolinska University Hospital Huddinge , Stockholm , Sweden.
authors.forename: Hassan
authors.initials: H
authors.lastname: Abolhassani
authors.affiliation: c Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences , University of Brescia, Spedali Civili , Brescia , Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Vitali
authors.affiliation: c Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences , University of Brescia, Spedali Civili , Brescia , Italy.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.affiliation: c Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences , University of Brescia, Spedali Civili , Brescia , Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giliani
authors.affiliation: a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Nima
authors.initials: N
authors.lastname: Parvaneh
authors.affiliation: a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Parvaneh
authors.affiliation: a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Mirminachi
authors.affiliation: d Department of Pediatrics , 17th Shahrivar Children's Hospital, Guilan University of Medical Sciences , Rasht , Iran.
authors.forename: Taher
authors.initials: T
authors.lastname: Cheraghi
authors.affiliation: e Department of Immunology and Hematology , Zahedan Medical, Sciences University , Zahedan , Iran.
authors.forename: Hosseinali
authors.initials: H
authors.lastname: Khazaei
authors.affiliation: f Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases , Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Seyed Alireza
authors.initials: SA
authors.lastname: Mahdaviani
authors.affiliation: a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Kiaei
authors.affiliation: a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Naiimeh
authors.initials: N
authors.lastname: Tavakolinia
authors.affiliation: g Department of Life Science, Faculty of New Science and Technology , University of Tehran , Tehran , Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Mohammadi
authors.affiliation: h School of Advanced Technologies in Medicine, Department of Medical Biotechnology , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Negahdari
authors.affiliation: a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
authors.affiliation: b Division of Clinical Immunology, Department of Laboratory Medicine , Karolinska Institutet at Karolinska University Hospital Huddinge , Stockholm , Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarstrom
authors.affiliation: c Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences , University of Brescia, Spedali Civili , Brescia , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.affiliation: a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Asghar
authors.initials: A
authors.lastname: Aghamohammadi
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics*; D001402:B-Lymphocytes / Q000502:physiology*; D025063:Chromosome Disorders; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005838:Genotype; D007070:Immunoglobulin A / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D007492:Iran; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D013997:Time Factors
chemical_list: D007070:Immunoglobulin A; D007148:Immunoglobulin mu-Chains; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase
keywords: Autosomal recessive agammaglobulinemia; Bruton’s tyrosine kinase; Genotype-phenotype correlation; Long-term cohort; X-linked agammaglobulinemia