Key result
A homozygous G-to-T mutation causing exon 17 skipping in the CLCN1 gene abolished chloride currents in vitro and led to recessive myotonia congenita in two unrelated patients.
Case Report (n=2)
A homozygous point mutation leading to exon 17 skipping in CLCN1 abolishes chloride current, causing recessive myotonia congenita.
Supports CLCN1 exon 17 screening in suspected myotonia congenita; leaves open validation in larger cohorts.
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.
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Chen et al. (2004) conducted a case report in Myotonia congenita (n=2). Homozygous G-to-T mutation on the donor splice site of intron 17 in CLCN1 (exon 17 skipping) vs. Wild-type channel was evaluated on Chloride current function and clinical phenotype. A homozygous G-to-T mutation causing exon 17 skipping in the CLCN1 gene abolished chloride currents in vitro and led to recessive myotonia congenita in two unrelated patients.
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