Identification of three novel mutations in the major human skeletal muscle chloride channel gene (CLCN1), causing myotonia congenita.

R. Brugnoni, S. Galantini, P. Confalonieri, M. R. Balestrini, F. Cornelio, R. Mantegazza

Research output: Contribution to journalArticle

Abstract

Myotonia congenita (MC) is a genetic disease characterized by mutations in the CLCN1 gene (OMIM*118425) encoding the skeletal muscle voltage-gated chloride channel (ClC-1). Autosomal dominant and recessive forms are observed, characterized by impaired muscle relaxation after forceful contraction (myotonia), which is more pronounced after inactivity and improves with exercise. We report three novel and one known mutations of the CLCN1 gene in four unrelated MC families. In two families the mutations were missense: 803C>T (T268M) and 1272C>G (I424M) in exons 7 and 12, respectively. The third was a splice mutation in intron 5 (696+2T>A), which induced a frame shift with a stop codon in exon 6 (fs213X). In the fourth family the previously-reported missense mutation 689G>A (G230E) was found. We also report two known polymorphisms: 261C>T (T87T) and 2154T>C (D718D) in exons 2 and 17 of two MC families; also found in 14 (33%) and 28 (67%) of 42 healthy controls, respectively. These findings expand our knowledge of mutations responsible for myotonia congenita, reducing the proportion of MC patients in whom genetic alterations have not been found.

Original languageEnglish
Pages (from-to)447
Number of pages1
JournalHuman Mutation
Volume14
Issue number5
Publication statusPublished - Nov 1999

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Myotonia Congenita
Chloride Channels
Skeletal Muscle
Mutation
Exons
Genes
Missense Mutation
Myotonia
Genetic Databases
Inborn Genetic Diseases
Muscle Relaxation
Terminator Codon
Introns
Exercise

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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Identification of three novel mutations in the major human skeletal muscle chloride channel gene (CLCN1), causing myotonia congenita. / Brugnoni, R.; Galantini, S.; Confalonieri, P.; Balestrini, M. R.; Cornelio, F.; Mantegazza, R.

In: Human Mutation, Vol. 14, No. 5, 11.1999, p. 447.

Research output: Contribution to journalArticle

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