Exon 17 skipping in CLCN1 leads to recessive myotonia congenita.
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.
Chen
Lie
L
Departments of Neurology and Clinical Research, Laboratory of Neuromorphology, University of Berne, Berne, Switzerland.
Schaerer
Martin
M
Lu
Zen H
ZH
Lang
Doris
D
Joncourt
Franziska
F
Weis
Joachim
J
Fritschi
Juerg
J
Kappeler
Lilianne
L
Gallati
Sabina
S
Sigel
Erwin
E
Burgunder
Jean-Marc
JM
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
C086321:CLC-1 channel; D018118:Chloride Channels