Análisis de ligamiento en una familia multigeneracional extendida que segrega para epilepsia idiopática / Linkage analysis in an extended multigenerational family segregating for idiopathic epilepsy

RESUMEN

Introducción. Los análisis de ligamiento permiten identificar loci que confieren susceptibilidad a diversas enfermedades de las que se presume una etiología genética, mediante la determinación de la cosegregación de alelos de marcadores específicos dentro de las familias. Objetivo. Determinar si existe susceptibilidad para desarrollar epilepsia idiopática generalizada (EIG) en las regiones 8q22.1 -q24.23, 16p13.3 y 21q22.3 en una familia multigeneracional extendida perteneciente a la comunidad Paisa de Antioquia, una población aislada genéticamente localizada en Colombia que segrega para EIG y con una gran potencialidad para detectar ligamiento. Pacientes y métodos. Se selecciona una familia con múltiples individuos afectados de epilepsia idiopática que consultaron al Instituto Neurológico de Antioquia. El individuo afectado debía tener un diagnóstico realizado por un neurólogo de epilepsia idiopática no mioclónica o de epilepsia idiopática parcial. Se realizó una videomonitorización a todos los pacientes con sospecha de epilepsia idiopática, con el fin de caracterizar electroencefalográficamente las crisis. Resultados. De los 106 individuos en esta familia incluidos en la genealogía, se genotipificaron 76, de los que 15 estaban afectados de crisis tonicoclónicas generalizadas y seis se consideraron posiblemente afectados. Los resultados de lod score son significativamente negativos para todos los marcadores con relación a cada modelo considerado. Conclusiones. Se descarta que los genes localizados en las regiones 8q22.1 -q24.23, 16p13.3 y 21q22.3 sean los responsables de la agregación familiar de la EIG en esta familia, como lo han sugerido estudios anteriores en otras familias (AU)

ABSTRACT

Introduction. Linkage analyses enable us to identify the loci that bestow susceptibility to certain diseases which are assumed to have a genetic aetiology by determining the cosegregation of alleles of specific markers within families. Aims. The aim of this study was to determine whether there is generalised idiopathic epilepsy (GIE) susceptibility in the 8q22.1 -q24.23, 16p13.3 and 21q22.3 regions within an extended multigenerational family belonging to the Paisa community in Antioquia, a genetic isolate located in Colombia segregating for GIE with a strong capacity for detecting linkage. Patients and methods. A family with a number of individuals affected by idiopathic epilepsy who visited the Instituto Neurológico de Antioquia was selected for study. An affected individual was required to have been diagnosed by a neurologist as suffering from nonmyoclonic idiopathic epilepsy or partial idiopathic epilepsy. All patients suspected of suffering from idiopathic epilepsy were submitted to video monitoring in order to characterise the seizures electroencephalographically. Results. Of the 106 individuals in this family that were included in the family tree, 76 were genotyped, 15 of whom were affected by generalised clonic tonic seizures and six were considered to be possibly affected. Results of the lod score were significantly negative for all the markers in relation to each model that was considered. Conclusions. The possibility of the genes located in the 8q22.1 -q24.23, 16p13.3 and 21q22.3 regions being responsible for the familial aggregation of GIE in this family was ruled out, which is in accordance with claims made in previous studies conducted on other families (AU)