Bruton tyrosine kinase gene mutations in Argentina.
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.
Danielian
Silvia
S
Molecular Biology Laboratory, Hospital Nacional de Pediatria J.P. Garrahan, Buenos Aires, Argentina. silviadanielian@yahoo.com.ar
El-Hakeh
Jazmin
J
Basílico
Guillermo
G
Oleastro
Matías
M
Rosenzweig
Sergio
S
Feldman
Guillermina
G
Berozdnik
Liliana
L
Galicchio
Miguel
M
Gallardo
Angela
A
Giraudi
Vera
V
Liberatore
Diana
D
Rivas
Eva Maria
EM
Zelazko
Marta
M
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*
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human