De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy.

ABSTRACT: Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six isolated patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative e

SUBMITTER: Syrbe S 

PROVIDER: S-EPMC4380508 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature