Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia

A patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy was sequenced by whole-exome sequencing, revealing a homozygous variant in KCNA1. This newly identified variant is the first to be reported to act in a recessive mode of inheritance in this gene. Functional analysis showed that mutant protein alone failed to produce functional channels, while coexpression with wild-type produced no effects on K+ currents, similar to wild-type protein alone. These findings serve as a cautionary tale for the diagnosis of channelopathies, in which an unreported phenotypic presentation or mode of inheritance can hinder the identification of causative variants. (By Dr. Edgard Verdura,, https://jmg.bmj.com/content/early/2019/10/05/jmedgenet-2019-106373 )

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