Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia.

ABSTRACT:

Background

Since 1994, over 50 families affected by the episodic ataxia type 1 disease spectrum have been described with mutations in KCNA1, encoding the voltage-gated K⁺ channel subunit Kv1.1. All of these mutations are either transmitted in an autosomal-dominant mode or found as de novo events.

Methods

A patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy was sequenced by whole-exome sequencing (WES). A candidate variant was tested using cellular assays and patch-clamp recordings.

Results

WES revealed a homozygous variant (p.Val368Leu) in KCNA1, involving a conserved residue in the pore domain, close to the selectivity signature sequence for K⁺ ions (TVGYG). Functional analysis s

SUBMITTER: Verdura E 

PROVIDER: S-EPMC7029237 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature