Correlation Analysis of Mutation Severity and BTK-expression by Clinical Manifestations in Patients with X-linked Agammaglobulinemia

Document Type: Original Article


1 Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran

2 Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.


Backgrounds/Objectives: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene. It is characterized by severely reduced numbers of peripheral B cells and a significant deficiency in all serum immunoglobulins. In the present study, the impact of mutation severity on the clinical and immunological characteristics of XLA patients was evaluated.
Methods: Mutation analysis was performed in 19 XLA patients by PCR assay to identify variations in theBTK gene. Subsequently, the western blotting technique was applied for measuring BTKexpression and function. A genotype-phenotype correlation was investigated regarding the impact of mutation severity on clinical and immunological parameters.
Results: Mutation detection in theBTK gene revealed missense mutations in 9 patients, nonsense mutations in 3 cases, splicing site defects in 5 patients, and small in-frame deletions in 2 patients; 31% of patients displayed normal BTK expression. A significant correlation was found between types of BTK mutation and BTK expression.
Discussion: Generally, genotype-phenotype correlation studies on XLA disease seem to be very controversial. The results of the correlation analysis in the present study could indicate that evolution of the disorder is not completely similar in all cases, even with the same mutation.