Gain-of-function KCNJ6 Mutation in a Severe Hyperkinetic Movement Disorder Phenotype.

ABSTRACT: Here, we describe a fourth case of a human with a de novo KCNJ6 (GIRK2) mutation, who presented with clinical findings of severe hyperkinetic movement disorder and developmental delay, similar to the Keppen-Lubinsky syndrome but without lipodystrophy. Whole-exome sequencing of the patient's DNA revealed a heterozygous de novo variant in the KCNJ6 (c.512T>G, p.Leu171Arg). We conducted in vitro functional studies to determine if this Leu-to-Arg mutation alters the function of GIRK2 channels. Heterologous expression of the mutant GIRK2 channel alone produced an aberrant basal inward current that lacked G protein activation, lost K⁺ selectivity and gained Ca²⁺ permeability. Notably, the inward current was inhibited by the Na⁺ channel blocker QX-314, similar to

SUBMITTER: Horvath GA 

PROVIDER: S-EPMC6679957 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature