Cohort of Iranian Patients with Congenital Agammaglobulinemia: Mutation Analysis and Novel Gene Defects

Expert Rev Clin Immunol. 2016;12(4):479-86. doi: 10.1586/1744666X.2016.1139451. Epub 2016 Feb 24.

Abstract

Objectives: 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.

Conclusion: 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.

Keywords: Autosomal recessive agammaglobulinemia; Bruton’s tyrosine kinase; Genotype-phenotype correlation; Long-term cohort; X-linked agammaglobulinemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / genetics*
  • B-Lymphocytes / physiology*
  • Chromosome Disorders
  • Cohort Studies
  • DNA Mutational Analysis
  • Genetic Association Studies
  • Genetic Diseases, X-Linked / genetics*
  • Genotype
  • Immunoglobulin A / genetics*
  • Immunoglobulin mu-Chains / genetics*
  • Iran
  • Mutation / genetics
  • Phenotype
  • Protein-Tyrosine Kinases / genetics*
  • Time Factors

Substances

  • Immunoglobulin A
  • Immunoglobulin mu-Chains
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase

Supplementary concepts

  • Bruton type agammaglobulinemia