A novel N440K sodium channel mutation causes myotonia with exercise-induced weakness--exclusion of CLCN1 exon deletion/duplication by MLPA

Acta Myol. 2011 Oct;30(2):133-7.

Abstract

We report a 4-generation Turkish family with 10 affected members presenting with myotonia and potassium- and exercise-induced paralytic attacks. The clinical presentation was neither typical for the chloride channel myotonias Thomsen and Becker nor for the separate sodium channel myotonia entities potassium-aggravated myotonia, paramyotonia congenita, and hyperkalemic periodic paralysis. It is best described by a combination of potassium-aggravated myotonia and hyperkalemic periodic paralysis. We excluded exonic chloride channel mutations including CLCN1 exon deletion/duplication by MLPA. Instead we identified a novel p.N440K sodium channel mutation that is located at the inner end of segment S6 of repeat I. We discuss the genotype phenotype relation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / therapeutic use
  • Anti-Arrhythmia Agents / therapeutic use
  • Anticonvulsants / therapeutic use
  • Chloride Channels / genetics*
  • Humans
  • Hyperkalemia / complications*
  • Hyperkinesis / complications*
  • Hyperkinesis / physiopathology
  • Muscle Weakness / etiology
  • Muscle Weakness / physiopathology
  • Muscle, Skeletal / physiopathology
  • Myotonia Congenita / drug therapy
  • Myotonia Congenita / etiology
  • Myotonia Congenita / genetics*
  • Paralysis / etiology
  • Paralysis / physiopathology
  • Pedigree
  • Segmental Duplications, Genomic
  • Sequence Deletion
  • Severity of Illness Index
  • Sodium Channels / genetics*

Substances

  • Anti-Arrhythmia Agents
  • Anticonvulsants
  • CLC-1 channel
  • Chloride Channels
  • Sodium Channels
  • Acetazolamide

Supplementary concepts

  • Potassium aggravated myotonia