title: Identification of three novel mutations in the major human skeletal muscle chloride channel gene (CLCN1), causing myotonia congenita.
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.
authors.affiliation: Department of Neuromuscular Diseases, National Neurological Institute "C. Besta", Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Brugnoni
authors.forename: S
authors.initials: S
authors.lastname: Galantini
authors.forename: P
authors.initials: P
authors.lastname: Confalonieri
authors.forename: M R
authors.initials: MR
authors.lastname: Balestrini
authors.forename: F
authors.initials: F
authors.lastname: Cornelio
authors.forename: R
authors.initials: R
authors.lastname: Mantegazza
mesh_terms: D018118:Chloride Channels / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009224:Myotonia Congenita / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels