Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate.

ABSTRACT: Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K⁺ current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP₂). Kv7.2 gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial neonatal seizures to severe early-onset epileptic encephalopathy (Kv7.2-EE). In this study, the biochemical and functional consequences prompted by a recurrent variant (R325G) found independently in four individuals with severe forms of neonatal-onset EE have been investigated. Upon heterologous expression, homomeric Kv7.2 R325G channels were non-functional, despite biotin-capture in Western blots revealed normal plasma membrane subunit expression. Mutant subunit

SUBMITTER: Soldovieri MV 

PROVIDER: S-EPMC5131271 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature