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Clin Neurophysiol. 2016 Jun;127(6):2503-8. doi: 10.1016/j.clinph.2016.03.008. Epub 2016 Mar 17.

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

Author information

1
Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
2
Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
3
Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
4
Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Department of Neurology, Qilu Hospital, Shandong University, Jinan, China. Electronic address: lpfsdu@foxmail.com.
5
Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Department of Neurology, Qilu Hospital, Shandong University, Jinan, China. Electronic address: chuanzhuyan@163.com.

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.

KEYWORDS:

Gene mutation; Hypokalemic periodic paralysis; KCNJ18 gene; Kir2.6; Thyrotoxic periodic paralysis

PMID:
27178871
DOI:
10.1016/j.clinph.2016.03.008
[Indexed for MEDLINE]

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