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Muscle Nerve. 2004 May;29(5):670-6.

Exon 17 skipping in CLCN1 leads to recessive myotonia congenita.

Author information

1
Departments of Neurology and Clinical Research, Laboratory of Neuromorphology, University of Berne, Berne, Switzerland.

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.

PMID:
15116370
DOI:
10.1002/mus.20005
[Indexed for MEDLINE]

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