Myotonia levior is a chloride channel disorder

Frank Lehmann-horn*, Volker Mailänder, Roland Heine, Alfred L. George

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

The group of dominant non-dystrophic myotonias, comprising disorders characterized by clinically similar forms of myogenic muscle stiffness, is genetically inhomogeneous. Dominant myotonia congenita (Thomsen's disease) is linked to CLCN1, the gene encoding the major muscle chloride channel, localized on chromosome 7q35. In contrast, dominant myotonias sensitive to potassium are caused by point mutations in SCN4A on chromosome 17q, the gene for the α subunit of the adult skeletal muscle sodium channel. No linkage or molecular genetic data are as yet available on 'myotonia levior' characterized by milder symptoms and later onset of myotonia than in Thomsen's disease, and absence of muscle hypertrophy. We report a CLCN1 Gln-552-Arg substitution for a family with dominant inheritance previously diagnosed to have myotonia levior. Thus, this disorder appears as a variant of Thomsen's disease due to mutations leading to low clinical expressivity. In addition, we report a novel IIe-290-Met CLCN1 mutation for a typical Thomsen pedigree. In another family previously diagnosed as having Thomsen's disease, we unexpectedly found a CLCN1 14 bp deletion known to cause recessive myotonia, and a rare Trp-118-Gly polymorphism.

Original languageEnglish (US)
Pages (from-to)1397-1402
Number of pages6
JournalHuman molecular genetics
Volume4
Issue number8
DOIs
StatePublished - Aug 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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