Mutations of Bruton's tyrosine kinase gene in Brazilian patients with X-linked agammaglobulinemia

V.D Ramalho,S.M Tani,E.B Oliveira Júnior,P Roxo Júnior,M.M.S Vilela

doi:10.1590/s0100-879x2010007500079

Abstract

Mutations in Bruton's tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA), which is characterized by recurrent bacterial infections, profound hypogammaglobulinemia, and decreased numbers of mature B cells in peripheral blood. We evaluated 5 male Brazilian patients, ranging from 3 to 10 years of age, from unrelated families, whose diagnosis was based on recurrent infections, markedly reduced levels of IgM, IgG and IgA, and circulating B cell numbers <2%. BTK gene analysis was carried out using PCR-SSCP followed by sequencing. We detected three novel (Ala347fsX55, I355T, and Thr324fsX24) and two previously reported mutations (Q196X and E441X). Flow cytometry revealed a reduced expression of BTK protein in patients and a mosaic pattern of BTK expression was obtained from mothers, indicating that they were XLA carriers.

Highlights

X-linked agammaglobulinemia (XLA, MIM# 300755) is a rare genetic disorder, which accounts for approximately 85% of patients with defects in early B cell development [1]
XLA is characterized by a marked reduction in all serum immunoglobulin isotypes with significantly decreased or absent B cells, which causes susceptibility to recurrent and severe bacterial infections in affected males
In 1993, the gene causing XLA was identified as Bruton’s tyrosine kinase (BTK) [2,3], which is localized on Xq21.3Xq22

Summary

Introduction

X-linked agammaglobulinemia (XLA, MIM# 300755) is a rare genetic disorder, which accounts for approximately 85% of patients with defects in early B cell development [1]. XLA is characterized by a marked reduction in all serum immunoglobulin isotypes with significantly decreased or absent B cells, which causes susceptibility to recurrent and severe bacterial infections in affected males. In 1993, the gene causing XLA was identified as Bruton’s tyrosine kinase (BTK) [2,3], which is localized on Xq21.3Xq22. More than 800 mutations in BTK have been described and have been found in all domains, being spread throughout the gene (http://bioinf.uta.fi/BTKbase) [5].

Results

Conclusion