J Korean Med Sci.  2005 Feb;20(1):162-165. 10.3346/jkms.2005.20.1.162.

A Korean Family of Hypokalemic Periodic Paralysis with Mutation in a Voltage-gated Calcium Channel (R1239G)

• Kim JB
• Lee KY
• Hur JK

• KMID: 1781747
• DOI: http://doi.org/10.3346/jkms.2005.20.1.162

Abstract

Hypokalemic periodic paralysis (HOPP) is a rare disease characterized by reversible attacks of muscle weakness accompanied by episodic hypokalemia. Recent molecular work has revealed that the majority of familial HOPP is due to mutations in a skeletal muscle voltage-dependent calcium-channel: the dihydropyridine receptor. We report a 13-yr old boy with HOPP from a family in which 6 members are affected in three generations. Genetic examination identified a nucleotide 3705 C to G mutation in exon 30 of the calcium channel gene, CACNA1S. This mutation predicts a codon change from arginine to glycine at the amino acid position #1239 (R1239G). Among the three known mutations of the CACNA1S gene, the R1239G mutation was rarely reported. This boy and the other family members who did not respond to acetazolamide, showed a marked improvement of the paralytic symptoms after spironolactone treatment.

Keyword

Hypokalemic Periodic Paralysis; Calcium Channels; Mutation; Spironolactone; Children

MeSH Terms

Acetazolamide/pharmacology
Adolescent
Arginine/chemistry
Calcium Channels/chemistry/*genetics
Codon
Exons
Family Health
Female
Glycine/chemistry
Humans
Hypokalemia/metabolism
Hypokalemic Periodic Paralysis/*diagnosis/*genetics
Korea
Male
Muscle, Skeletal/metabolism
Mutation
Pedigree
Protein Structure, Tertiary
Sequence Analysis, DNA
Spironolactone/pharmacology

Figure

• 

  Fig. 1 Pedigree of the HOPP family. The dark symbols are affected individuals. The proband is indicated by an arrow. The age of the family members is designated by the number.

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  Fig. 2 Schematic diagram of the DHP receptor α1-subunit composed of four domains of an internal homology (DI to DIV) connected by intracellular loops. The R1239G mutation substitutes a positively-charged arginine located within segment DIVS4 by a neutral glycine.

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