noncoding mutation

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder characterized by recurrent bacterial infections, profound lack of serum antibodies and reduced circulating B lymphocytes. Mutations in Bruton´s tyrosine kinase gene (BTK) result in XLA. It is shown that absence of Btk protein expression may be accompanied by no mutations in coding regions in some cases, instead alterations in conserved regulatory domains of promoter and the first intron of BTK gene maybe occurred. The aim of this study was evaluation of Btk expression and mutation analysis in coding and regulatory regions of the gene. In this study, eleven XLA patients were enrolled. Btk expression was analyzed by western immunoblotting method. Mutation analysis was carried out in eight patients. In three cases, PCR of the regulatory regions was performed with designed primers, followed by sequencing. According to western blot, normal Btk expression in three patients and null expression in eight others was observed. Mutation analysis showed two novel BTK mutations in two patients (1038-1040 delAGG and IVS8-2delA). No coding or regulatory region mutations were found in three cases with null Btk expression. Based on these results, three cases with null expression and had no coding or regulatory region mutations are interesting. It is possible that some rare regulatory defects may have been occurred, other than conventional sites. This must be taken into account for future investgations.