title: [Detection of Bruton's tyrosine kinase gene mutations and clinical analysis of 6 patients with X-linked agammaglobulinemia].
abstract: OBJECTIVE
  To explored the relationship between genotype of Bruton's tyrosine kinase (BTK) gene and X-linked agammaglobulinemia (XLA).
  
  
  METHODS
  Six 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.
  
  
  RESULTS
  All 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.
  
  
  CONCLUSIONS
  Detection 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.
authors: Department of Pediatric Hematology and Oncology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R.China. 18681373671@163.com.
authors: Xiaomin
authors: X
authors: Zhang
authors: Hong
authors: H
authors: Li
authors: Qiang
authors: Q
authors: Li
authors: Ju
authors: J
authors: Gao
authors: Xiaoqing
authors: X
authors: Shi
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology* / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000201:enzymology* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human