Referenced in: none

Automatically associated channels: ClC1 , ClC4

Title: Exon 17 skipping in CLCN1 leads to recessive myotonia congenita.

Authors: Lie Chen, Martin Schaerer, Zen H Lu, Doris Lang, Franziska Joncourt, Joachim Weis, Juerg Fritschi, Lilianne Kappeler, Sabina Gallati, Erwin Sigel, Jean-Marc Burgunder

Journal, date & volume: Muscle Nerve, 2004 May , 29, 670-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15116370

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.