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

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.

• Authors: F Lehmann-Horn, M Orth, M Kuhn, K Jurkat-Rott
• Journal: Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology (Acta Myol) Vol. 30 Issue 2 Pg. 133-7 (Oct 2011) ISSN: 1128-2460 [Print] Italy
• PMID: 22106717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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