title: Genotype-phenotype correlation in Bruton's tyrosine kinase deficiency.
abstract: Bruton's tyrosine kinase (Btk) belongs to the Tec family of nonreceptor protein tyrosine kinases. Mutations in the BTK gene cause X-linked agammaglobulinemia (XLA); a primary immunodeficiency disorder in human. No clear genotype-phenotype correlation has been established in XLA so far. To determine how differently mutations in BTK affect the severity of the disease and if BTK promoter polymorphic variant or intron 1 polymorphic variant in Tec, a cytoplasmic tyrosine kinase that might substitute for Btk, could contribute to the clinical phenotype, we analyzed the clinical and molecular findings in a cohort of XLA patients. Polymorphisms in BTK promoter and TEC intron 1 regions include substitutions of C>T (rs2071219) and T>C (rs2664019), respectively. Btk expression was evaluated by means of western immunoblotting and fluorescence-activated cell sorter analysis. Mutations were categorized as mild or severe and patients were evaluated for the clinical severity of disease. On the basis of the results, severe genotypes do not necessarily lead to severe phenotypes. More over, in a considerable number of patients with mild phenotype we showed a severe mutation with a tendency toward C substitution in the polymorphic site on TEC intron 1.
authors.affiliation: Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran. teimourian@tums.ac.ir
authors.forename: Shahram
authors.initials: S
authors.lastname: Teimourian
authors.forename: Saeed
authors.initials: S
authors.lastname: Nasseri
authors.forename: Nima
authors.initials: N
authors.lastname: Pouladi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yeganeh
authors.forename: Asghar
authors.initials: A
authors.lastname: Aghamohammadi
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005192:Family Health; D040181:Genetic Diseases, X-Linked; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D012720:Severity of Illness Index
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human