Myoclonus epilepsy and ataxia due to : Analysis of 20 cases and K+ channel propertiesKCNC: Analysis of 20 cases and K+ channel properties1: Analysis of 20 cases and K+ channel properties mutation: Analysis of 20 cases and K+ channel properties
Some of the disorders have a geographical concentration, such as ULD in Finland and around the Mediterranean, AMRF in Quebec, DRPLA in Japan, and North Sea PME in the Netherlands, Denmark, and northern Germany. In carefully studied cohorts, a specific diagnosis can be reached in 70 to 90% of PME patients.2
To address the residuum that defied molecular diagnosis, we formed an international consortium to collect, characterize, and perform whole exome sequencing (WES) on a cohort of 84 hitherto unsolved PME patients. Interrogation of WES data resulted in the discovery of a mutation in the potassium (K+) channel gene KCNC1,14 a gene not previously associated with human disease, which encodes the voltage‐dependent K+ channel KV3.1. Remarkably, the exact same heterozygous missense change (p.R320H) was found in multiple unrelated patients, the majority of whom were sporadic cases due to de novo mutation. The mutation was shown to have a dominant‐negative loss‐of‐function effect when the KV3.1 channel was analyzed in vitro.14
Here, we describe in detail the clinical, electrophysiological, and imaging features of this novel disorder, known as myoclonus epilepsy and ataxia due to K+ channel mutation (MEAK),14 in 20 patients. Furthermore, we performed additional in vitro electrophysiological studies aimed at exploring the clinical observation of improvement with fever.