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¿Una variante recesiva del síndrome del intervalo QT largo de Romano-Ward?
S G Priori1, P J Schwartz, C Napolitano
1Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, Milan, Italy.
Circulation
|June 26, 1998
Resumen
Se identificó una rara forma recesiva del síndrome de Romano-Ward de QT largo, causada por una mutación homocigótica del gen KVLQT1. Este hallazgo sugiere que las mutaciones leves pueden predisponer a las personas a las arritmias, incluso sin el síndrome de Jervell y Lange-Nielsen.
Área de la Ciencia:
- Genética La genética.
- Cardiología Cardiología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- El síndrome congénito de QT largo (LQTS) es un trastorno genético heterogéneo que causa arritmias cardíacas peligrosas.
- Las mutaciones en el gen KVLQT1, que codifica un canal de potasio cardíaco, conducen a los síndromes de Romano-Ward (dominante) o Jervell y Lange-Nielsen (recesivos).
Objetivo del estudio:
- Para investigar la base genética de LQTS en una familia consanguínea con una presentación clínica distinta.
- Para caracterizar el impacto funcional de una nueva mutación KVLQT1.
Principales métodos:
- Cribado del gen KVLQT1 en una familia de LQTS consanguíneos.
- Expresión de ARN complementarios en los ovocitos de Xenopus.
- Registros electrofisiológicos utilizando la técnica del doble microelectrodo.
Principales resultados:
- En la prueba se identificó una mutación homocigótica de mal sentido (sustitución Ala-a-Thr) en el dominio poroso KVLQT1.
- La mutación redujo la corriente del canal, cambió la activación hiperpolarizada y aumentó la tasa de activación.
- Los padres heterocigotos exhibieron intervalos QT normales, lo que sugiere que la mutación requiere homocigosidad para manifestar LQTS.
Conclusiones:
- Este estudio presenta la primera evidencia de una forma recesiva de Romano-Ward LQTS.
- Las mutaciones homocigotas de KVLQT1 no siempre resultan en el síndrome de Jervell y Lange-Nielsen.
- Las mutaciones leves de KVLQT1 pueden contribuir a la susceptibilidad al LQTS y a las arritmias inducidas por fármacos en la población general.
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