RESUMO
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Assuntos
Masculino , Recém-Nascido , Humanos , Deficiência de Antitrombina III/complicações , Trombose/etiologia , Deficiência de Antitrombina III/genética , Trombose/genética , Testes de Coagulação Sanguínea/métodosRESUMO
La antitrombina es el principal anticoagulante hemostático. Desde que el hematólogo Egeber descubriera en 1965 la primera deficiencia de antitrombina asociada a un aumento del riesgo trombótico, numerosos trabajos han identificado familias con deficiencia de antitrombina asociada a una significativa incidencia de trombosis venosa. Este trabajo recoge el estudio de 3 familias trombofílicas españolas con deficienciacongénita de antitrombina. En dos identificamos mutaciones en el gen de la antitrombina no descritas hasta la fecha: InsT7429-30 y Lys125Arg. En la tercera detectamos una variante, la antitrombina Cambridge II (Ala384Ser) identificada con elevada frecuencia en población británica. Valoramos su frecuencia en población española y su papel en el desarrollode trombosis venosa mediante un estudio de asociación caso-control en 1018 pacientes de trombosis venosa y 1018controles. Comprobamos que la antitrombina Cambridge II es una alteración no restringida a población británica, estando presente en el 0.2% de la población española pero en un 1.7% de los pacientes con trombosis venosa. Así, el alelo mutado incrementó 9.75 veces el riesgo trombótico. Además, esta mutación es la principal causa de deficiencia de antitrombina en pacientes con trombosis venosa. Finalmente destacamos que la antitrombina Cambridge II únicamente puede ser detectada por métodos moleculares. Todos estos resultados aconsejan el estudio de la antitrombina Cambridge II en los estudios trombofílicos rutinarios
Antithrombin is the most important haemostatic anticoagulant. Since, in 1965 Egeber described the first antithrombin deficiency associated with an increase of thrombotic risk, many studies have identified families with antithrombin deficiency that caused a significantly increase in the risk of venous thrombosis. We studied three thrombofilic families with congenital antithrombin deficiency. In two of them, we identified mutations in antithrombin gene not described previously: InsT7429-30 and Lys125Arg. In the third family, we detected a variant, antithrombin Cambridge II (Ala384Ser) that had a high frequency in British population. We have evaluated the prevalence of this mutation in Spanish population, and its role in venous thrombosis in a case-control study including 1018 patients with venous thrombosis and 1018 healthy controls. We confirmed that antithrombin Cambridge II is not restricted to British population, as we observed this mutation in 0.2% of Spanish population and in 1.7% of patients with venous thrombosis. The mutated allele increased 9.75 fold the risk of venous thrombosis. Moreover, this mutation was the main cause of antithrombin deficiency among patients with venous thrombosis. Finally, we point that this variant can only be detected by molecular methods. All our data support the study of antithrombin Cambridge II in routine thrombophilic tests
Assuntos
Humanos , Masculino , Feminino , Adulto , Antitrombinas/genética , Deficiência de Antitrombina III/genética , Trombose Venosa/genética , Antitrombinas/deficiência , Trombose Venosa/etiologia , Mutação/genética , Trombofilia/genéticaRESUMO
The study of the organization of immunoglobulin and T cell receptor genes in leukaemias and lymphomas depends on our ability to obtain high molecular weight DNA. We have compared two different methods of DNA extraction: one being enzymatic, using the enzyme proteinase K, and the other chemical, using urea as a substance purifying DNA. Since the amount and purity of the DNA obtained are similar with each of the two methods of DNA extraction, both are valid to make such a genetic analysis.
