Correlation of Null Btk Expression and Gene Noncoding Mutations in XLA Patients Nasseri S1, Sorouri R2, Pourpak Z3, Rezaei N4, Moin M5, Parvaneh N6, Aghamohammadi A7 1 Dept of Molecular Biology, Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran 2 Baqiyatallah University of Medical Sciences, Tehran, Iran and, Zanjan University of Medical Sciences, Zanjan, Iran 3 Dept of Immunology, Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran 4 Dept of Immunology, Immunology, Asthma and Allergy Research Institute and Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran 5 Dept of Immunology, Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran 6 Dept of Infectious Diseases, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran 7 Section of Immunology and Allergy, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran Corresponding Author's Address: Section of Immunology and Allergy, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran E-mail: aghamohammadi@sina.tums.ac.ir Received: 20 July, 2008 Accepted: 29 Dec, 2008 Background and Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.