OBJECTIVETo explored the relationship between genotype of Bruton's tyrosine kinase (BTK) gene and X-linked agammaglobulinemia (XLA).

METHODSSix patients who were clinically suspected as XLA based on immunological results were studied. Peripheral blood samples were collected for DNA extraction. The 19 exons and exon-intron boundaries of the BTK gene were amplified by PCR, and the products were directly sequenced.

RESULTSAll of the 6 patients were confirmed to have XLA due to the mutations in exons of the BTK gene. Among these, 3 mutations were located in the kinase domain (TK), 2 were located in pleckstrin homology (PH) domain, and 1 was located in Src homology (SH2) domain. The mutations have included 3 missense mutations, i.e., c.1105C to T (p.L369F), c.82C to T(p.R28C) and c.1754T to C (p.V585A), 2 nonsense mutations, i.e., c.1834C to T (p.Q612X) and c.37C to T (p.R13X). One patient was found to have complex (missense and nonsense) mutations, i.e., c.1802-1803TT to GC (p.F601C) and c.1803-1804insC (p.T602fsX603). There were 3 novel mutations (p.F601C, p.T602fsX603 and p.V585A). The mothers of 5 patients were also detected with BTK gene mutations, among whom 4 were demonstrated to be carriers and one was normal (her son had p.V585A mutation). Therefore, p.V585A was a de novo mutation.

CONCLUSIONDetection of BTK gene mutation can confirm clinical diagnosis which is critical for patients to take regular immunoglobulin replacement therapy for life. Early genetic diagnosis can also identify carriers and make genetic counseling possible.