title: Exon 17 skipping in CLCN1 leads to recessive myotonia congenita.
abstract: Mutations in CLCN1, the gene encoding the ClC-1 chloride channel in skeletal muscle, lead to myotonia congenita. The effects on the intramembranous channel forming domains have been investigated more than that at the intracellular C-terminus. We have performed a mutation screen involving the whole CLCN1 gene of patients with myotonia congenita by polymerase chain reaction (PCR), single-strand conformation polymorphism studies, and sequencing. Two unrelated patients harbored the same homozygous G-to-T mutation on the donor splice site of intron 17. This led to the skipping of exon 17, as evidenced by the reverse transcriptase PCR. When the exon 17-deleted CLCN1 was expressed in Xenopus oocytes, no chloride current was measurable. This function could be restored by coexpression with the wild-type channel. Our data suggest an important role of this C-terminal region and that exon 17 skipping resulting from a homozygous point mutation in CLCN1 can lead to recessive myotonia congenita.
authors.affiliation: Departments of Neurology and Clinical Research, Laboratory of Neuromorphology, University of Berne, Berne, Switzerland.
authors.forename: Lie
authors.initials: L
authors.lastname: Chen
authors.forename: Martin
authors.initials: M
authors.lastname: Schaerer
authors.forename: Zen H
authors.initials: ZH
authors.lastname: Lu
authors.forename: Doris
authors.initials: D
authors.lastname: Lang
authors.forename: Franziska
authors.initials: F
authors.lastname: Joncourt
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Juerg
authors.initials: J
authors.lastname: Fritschi
authors.forename: Lilianne
authors.initials: L
authors.lastname: Kappeler
authors.forename: Sabina
authors.initials: S
authors.lastname: Gallati
authors.forename: Erwin
authors.initials: E
authors.lastname: Sigel
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Burgunder
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018118:Chloride Channels / Q000096:biosynthesis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D008297:Male; D009224:Myotonia Congenita / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics; D014982:Xenopus laevis
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels