E2. When we work up a new-onset epileptic encephalopathy in clinical practice, there is a discrepancy between what we know and what we do. While we know that we have an almost 30% chance to find a causative de novo mutation in any of the known epilepsy genes, we usually think about a possible underlying inherited metabolic disorder when we order our first round of tests. However, the full phenotypic spectrum is often unknown and the question remained how many of these inherited metabolic disorders are missed. In our recent publication of the E2 consortium, we looked for evidence of inherited genetic disorders in patients with epileptic encephalopathies. Follow us on our journey that led to a negative answer, but uncovered a complexity in finding inherited diseases that we did not anticipate. Continue reading
Tag Archives: E2 consortium
E2 – collaborations and lessons learnt
E2. The advent of next generation sequencing allowed unimagined scope for large scale genetic studies. It quickly became clear that whilst new technologies could be used to solve single families, major advances would only occur by collaboration. This led to the formation of a number of Consortia – in the United States EPGP leading onto Epi4K and in Europe EuroEPINOMICS and EpiRES etc as well as a number of smaller consortia. Even with these multicentre collaborations it was clear that “bigger was better”, and attempts were made to try and synergize efforts across continents. Continue reading
DNM1 encephalopathy – interneurons, endocytosis, and study group
Dynamin 1. De novo mutations in DNM1 coding for Dynamin 1 are increasingly recognized as a cause for epileptic encephalopathies. However, given the role of Dynamin 1 in endocytosis in a large number of cells, the precise mechanisms how mutations may result in seizures are poorly understood. Now two recent publications in PLOS Genetics and Neurology Genetics explore the functional effects of epilepsy-related DNM1 mutations. The publication of both manuscripts is also a timely reminder to announce our international DNM1 study group that has the aim to better understand the phenotype of this disease. Continue reading
