title: Clinical characteristics and genotype-phenotype correlation in 62 patients with X-linked agammaglobulinemia.
abstract: BACKGROUND
  X-linked agammagobulinemia (XLA) is a primary immunodeficiency disorder caused by Bruton's tyrosine kinase (Btk) gene mutation. Recent studies suggested genotype-phenotype correlation in XLA, but a definitive association remains controversial.
  
  
  METHODS
  We examined the relationship between specific Btk gene mutations and severity of clinical presentation in 62 patients with XLA. Disease severity was assessed by the age of disease onset and the presence of severe infections, while mutations were classified into severe and mild based on structural and functional consequence by bioinformatics analysis.
  
  
  RESULTS
  Fifty-six Btk mutations were identified in 62 patients from 57 kindreds. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset as well as occurrence of severe infections.
  
  
  CONCLUSIONS
  A critical analysis of the circumstances upon presentation also revealed that under-recognition of recurrent infections and relevant family history are important hurdles to timely diagnosis of XLA.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Pamela P W
authors.initials: PP
authors.lastname: Lee
authors.forename: Tong-Xin
authors.initials: TX
authors.lastname: Chen
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jiang
authors.forename: Koon-Wing
authors.initials: KW
authors.lastname: Chan
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.forename: Bee-Wah
authors.initials: BW
authors.lastname: Lee
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Chiang
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Chen
authors.forename: Susanna F S
authors.initials: SF
authors.lastname: Fok
authors.forename: Tsz-Leung
authors.initials: TL
authors.lastname: Lee
authors.forename: Marco H K
authors.initials: MH
authors.lastname: Ho
authors.forename: Xi-Qiang
authors.initials: XQ
authors.lastname: Yang
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007239:Infections / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D053632:X-Linked Combined Immunodeficiency Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human