RESUMO

Mutations in Bruton's tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA), which is characterized by recurrent bacterial infections, profound hypogammaglobulinemia, and decreased numbers of mature B cells in peripheral blood. We evaluated 5 male Brazilian patients, ranging from 3 to 10 years of age, from unrelated families, whose diagnosis was based on recurrent infections, markedly reduced levels of IgM, IgG and IgA, and circulating B cell numbers <2 percent. BTK gene analysis was carried out using PCR-SSCP followed by sequencing. We detected three novel (Ala347fsX55, I355T, and Thr324fsX24) and two previously reported mutations (Q196X and E441X). Flow cytometry revealed a reduced expression of BTK protein in patients and a mosaic pattern of BTK expression was obtained from mothers, indicating that they were XLA carriers.

Assuntos

Criança , Pré-Escolar , Humanos , Masculino , Agamaglobulinemia/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação/genética , Proteínas Tirosina Quinases/genética , Agamaglobulinemia/enzimologia , Citometria de Fluxo , Doenças Genéticas Ligadas ao Cromossomo X/enzimologia , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples

RESUMO

Mutations in Bruton's tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA), which is characterized by recurrent bacterial infections, profound hypogammaglobulinemia, and decreased numbers of mature B cells in peripheral blood. We evaluated 5 male Brazilian patients, ranging from 3 to 10 years of age, from unrelated families, whose diagnosis was based on recurrent infections, markedly reduced levels of IgM, IgG and IgA, and circulating B cell numbers <2%. BTK gene analysis was carried out using PCR-SSCP followed by sequencing. We detected three novel (Ala347fsX55, I355T, and Thr324fsX24) and two previously reported mutations (Q196X and E441X). Flow cytometry revealed a reduced expression of BTK protein in patients and a mosaic pattern of BTK expression was obtained from mothers, indicating that they were XLA carriers.

Assuntos

Agamaglobulinemia/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação/genética , Proteínas Tirosina Quinases/genética , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/enzimologia , Criança , Pré-Escolar , Citometria de Fluxo , Doenças Genéticas Ligadas ao Cromossomo X/enzimologia , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples