Protein and Genetic Analysis of Bruton's Tyrosine Kinase(Btk) in Three Korean X-linked gammaglobulinemia(XLA) Families

ABSTRACT

PURPOSE: Mutations in the Bruton's tyrosine kinase(Btk) gene are responsible for X-linked agammaglobulinemia(XLA), an immunodeficiency caused by a block in B cell differentiation. In this report we characterize the protein expression and genetic mutations of Btk in four Korean patients with three unrelated XLA families. METHODS: The resulting Btk proteins were characterized by a flow cytometry and the mutations were analyzed using single strand conformation polymorphism(SSCP) and direct sequencing. RESULTS: Two deletions, including one novel genetic alteration, and one splicing error, were found in these three XLA families. Along with the identification of mutations, Btk protein analysis using flow cytometry clearly showed cellular mosaicism in monocytes from five obligate carriers, findings consistent with those by SSCP. We attempted to determine the origin of mutation in an XLA family with a novel 4-bp deletion of exon eight, suggesting a germline mutation in this family. In addition, we found some clinical heterogeneities in the affected brothers with the same gene mutation. CONCLUSION: These identified genetic alterations provided valuable clues to the pathogenesis of XLA in Korea. The flow cytometric analysis is suggested as a useful tool for rapid detection of XLA patients and carriers.