Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange Factor DENND5A.

ABSTRACT: Epileptic encephalopathies are a catastrophic group of epilepsies characterized by refractory seizures and cognitive arrest, often resulting from abnormal brain development. Here, we have identified an epileptic encephalopathy additionally featuring cerebral calcifications and coarse facial features caused by recessive loss-of-function mutations in DENND5A. DENND5A contains a DENN domain, an evolutionarily ancient enzymatic module conferring guanine nucleotide exchange factor (GEF) activity to multiple proteins serving as GEFs for Rabs, which are key regulators of membrane trafficking. DENND5A is detected predominantly in neuronal tissues, and its highest levels occur during development. Knockdown of DENND5A leads to striking alterations in neuronal development. Mechanistically, these chan

SUBMITTER: Han C 

PROVIDER: S-EPMC5142110 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature