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Genetics of epileptic encephalopathies - from genotype-phenotype correlation to disease modeling in zebrafish

Dravet syndrome (DS) is a severe epilepsy disorder with a significant impact on the quality of life of both patient and parents. It is characterized by fever-sensitive epileptic seizures starting in the first year of life which are soon followed by mental decline. DS has a genetic cause and in ca. 80 % a causative genetic defect is found in the SCN1A gene. However, in remaining patients the causative genetic defect is still unknown. Currently our research group is analyzing research data of Whole Exome Sequencing on 28 SCN1Amutation- negative DS patients in a search to discover novel genes implicated in DS. We already identified some interesting candidate genes. The aim of my project is to select the most promising candidate genes and establish their causative character through functional validation studies. I will do this by studying the epilepsy phenotype in zebrafish modeling deficiency of these novel genes implicated in DS. Subsequently I will perform large follow-up studies on these novel genes, enabling me to formulate genotype-phenotype correlations. Discovery of additional genes involved in DS will have the immediate consequence that a correct, early diagnosis and genetic counselling can be offered to both physicians and parents. Moreover, functional validation in zebrafish will help us understand the pathophysiology of DS and may form a point of application for pharmacological studies which could uncover potential therapeutic strategies for this devastating disorder.
Date:1 Oct 2017  →  30 Sep 2019
Disciplines:Genetics, Systems biology, Molecular and cell biology
Project type:Collaboration project