A novel Kir2.6 mutation associated with hypokalemic periodic paralysis.

Abstract

BACKGROUND AND OBJECTIVE:

Mutations in KCNJ18, which encodes the inwardly rectifying potassium channel Kir2.6, have rarely been reported in hypokalemic periodic paralysis. We describe the clinical phenotype of a novel KCNJ18 gene mutation and perform functional characterization of this mutant Kir2.6.

METHODS:

A long-term exercise test (ET) was conducted based on the McManis method. Whole-cell currents were recorded using patch clamp, and the HEK293 cells were transfected with wild-type or/and mutant Kir2.6 cDNA.

RESULTS:

A de novo conserved heterozygous mutation in Kir2.6, G169R, was found in a hypokalemic periodic paralysis patient. ET led to a decrease in the amplitude of compound muscle action potential (CMAP) by 64%. Patch clamp results showed that the potassium inward and outward current densities of the G169R mutant were, respectively, reduced by 65.6% and 84.7%; for co-expression with wild type, which more closely resembles the physiological conditions in vitro, the inward and outward current densities decreased, respectively, by 48.2% and 47.4%.

CONCLUSIONS:

A novel KCNJ18 mutation, G169R, was first reported to be associated with hypokalemic periodic paralysis without hyperthyroidism. Electrophysiological results demonstrated a significant functional defect of this mutant, which may predispose patients with this mutation to paralysis.

SIGNIFICANCE:

This new G169R mutation of the potassium channel Kir2.6 provides insight into the pathogenic mechanisms of hypokalemic periodic paralysis.

• Authors: Jinfan Zheng, Zonglai Liang, Ying Hou, Fuchen Liu, Yuanyuan Hu, Pengfei Lin, Chuanzhu Yan
• Journal: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology (Clin Neurophysiol) Vol. 127 Issue 6 Pg. 2503-8 (06 2016) ISSN: 1872-8952 [Electronic] Netherlands
• PMID: 27178871 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Chemical References

• KCNJ18 protein, human
• Potassium Channels, Inwardly Rectifying

Topics

• Action Potentials
• Adult
• Animals
• COS Cells
• Chlorocebus aethiops
• HEK293 Cells
• Humans
• Male
• Mutation
• Paralysis, Hyperkalemic Periodic (genetics)
• Potassium Channels, Inwardly Rectifying (genetics)