title: Bruton tyrosine kinase gene mutations in Argentina.
abstract: The block in differentiation from pro-B to pre-B cells results in a selective defect in the humoral immune response characteristic of human X-linked agammaglobulinemia (XLA). Mutations of Bruton tyrosine kinase (BTK) gene have been identified as the cause of XLA. Mutation detection is the most reliable method for making a definitive diagnosis, except when clinical and laboratory findings are distinctive and coupled with history of X-linked inheritance. To provide a definitive diagnosis to 40 families incorporated in the Argentinian Primary Immunodeficiencies Registry we analysed the BTK gene by SSCP analysis as screening method for XLA, followed by direct sequencing. The molecular defect was localized in 45 patients from 34 unrelated families. From the 34 independent mutations identified, 16 were previously undescribed, 31 were unique mutations, 22 were exonic single nucleotide changes (16 missense and 6 nonsense) and four intronic mutations. Because five families had clinical, immunological and inheritance data sufficient for a definitive diagnosis, our study allowed 37 patients from 29 families previously categorized probable/ possible XLA, have now definitive diagnosis leading to appropriate genetic counseling.
authors.affiliation: Molecular Biology Laboratory, Hospital Nacional de Pediatria J.P. Garrahan, Buenos Aires, Argentina. silviadanielian@yahoo.com.ar
authors.forename: Silvia
authors.initials: S
authors.lastname: Danielian
authors.forename: Jazmin
authors.initials: J
authors.lastname: El-Hakeh
authors.forename: Guillermo
authors.initials: G
authors.lastname: Basílico
authors.forename: Matías
authors.initials: M
authors.lastname: Oleastro
authors.forename: Sergio
authors.initials: S
authors.lastname: Rosenzweig
authors.forename: Guillermina
authors.initials: G
authors.lastname: Feldman
authors.forename: Liliana
authors.initials: L
authors.lastname: Berozdnik
authors.forename: Miguel
authors.initials: M
authors.lastname: Galicchio
authors.forename: Angela
authors.initials: A
authors.lastname: Gallardo
authors.forename: Vera
authors.initials: V
authors.lastname: Giraudi
authors.forename: Diana
authors.initials: D
authors.lastname: Liberatore
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Rivas
authors.forename: Marta
authors.initials: M
authors.lastname: Zelazko
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D001118:Argentina / Q000453:epidemiology; D006580:Genetic Carrier Screening / Q000379:methods; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human