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A truncation mutation and excess variation in the CLCN1 gene were identified in patients with epilepsy, suggesting a novel role for the ClC-1 chloride channel in the brain.
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The findings suggest a novel role for the ClC-1 chloride channel in the brain and a potential link between myotonia and epilepsy.
Chen et al.1 report 2 novel findings: a truncation mutation in the CLCN1 gene, encoding the chloride channel protein ClC-1, in a patient with myotonic dystrophy and generalized epilepsy; and an excess of variation in CLCN1 in patients with epilepsy compared to controls. They also demonstrate expression of C1C-1 mRNA and protein in human brain autopsy specimens and mouse brain. Mutations in the CLCN1 gene have been long recognized as the cause of dominant (Thomsen-type) and recessive (Becker-type) myotonia but an association with epilepsy has not been reported. Until now it was believed that ClC-1 protein and channels were not expressed in the brain; therefore, the mutation would have no effect on the CNS. The patient reported in this study had generalized epilepsy and generalized seizures, which involve thalamocortical circuits. Interestingly, the authors found that ClC-1 mRNA was moderately expressed in the mouse thalamus and cortex. The clinical phenotype, combined with the animal data, strongly suggests a role for ClC-1 in the brain.
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Berkovic et al. (2013) conducted an editorial in Myotonia and epilepsy. CLCN1 gene mutation/variation vs. Controls was evaluated. A truncation mutation and excess variation in the CLCN1 gene were identified in patients with epilepsy, suggesting a novel role for the ClC-1 chloride channel in the brain.
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