title: Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China.
abstract: BACKGROUND
  X-Linked agammaglobulinemia is a prototypical humoral immunodeficiency with the mutation of the Bruton's tyrosine kinase gene.
  
  
  METHODS
  We investigated the gene mutation and clinical features of 30 Chinese X-linked agammaglobulinemia (XLA) patients from 27 families. There were 26 mutations, including 11 novel and 15 recurrent mutations, distributing over the entire gene. The nucleotide and amino acid aberration, 1129C>T(H333Y) and 1196T>A(I355N), in SH2 have not been reported before. Five (I355N, W124R, R520X, I590F, G594E) of the 24 mutations not detected in the mothers receiving gene analysis were determined to be de novo. Two mutations occurred within intronic splice-site sequences (intron5(-2)A>G, intron17(-2)A>T).
  
  
  CONCLUSIONS
  There are eight mutations in the PH domain, two mutations in the SH3 domain, three mutations in the SH2 domain, one mutation in the TH domain, and other 16 mutations in the TK domain. The mutations of protein domain is most common in TK (53%) domain and then in PH(8%) domain. Missense and nonsense mutations were found equal in 46% of the detected mutations. All of the patients are alive, but one died of liver cancer. Clinical features and serum Igs levels range variedly and were not correlated with genotypes. Our results demonstrated molecular genetic characteristics of XLA in mainland China.
authors.affiliation: Department of Clinical Immunology, Jeffrey Modell Diagnostic and Research Center, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Han
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shunying
authors.initials: S
authors.lastname: Zhao
authors.forename: Yeheng
authors.initials: Y
authors.lastname: Yu
authors.forename: Jingyi
authors.initials: J
authors.lastname: Wang
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009894:Opportunistic Infections / Q000150:complications / Q000276:immunology*; D011014:Pneumonia; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012852:Sinusitis; D053632:X-Linked Combined Immunodeficiency Diseases / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human