Novel CLCN1 mutations with unique clinical and electrophysiological consequences

Myotonia is a condition characterized by impaired relaxation of muscle following sudden forceful contrac-tion. We systematically screened all 23 exons of the CLCN1 gene in 88 unrelated patients with myotonia and identi®ed mutations in 14 patients. Six novel muta-tions were discovered: ®ve were missense (S132C, L283F, T310M, F428S and T550M) found in hetero-zygous patients, and one was a nonsense mutation (E193X) in a homozygous patient. While ®ve patients had a clinical diagnosis of myotonia congenita, the patient with the F428S mutation exhibited symptoms characteristic of paramyotonia congenitaÐa condition usually thought to be caused by mutations in the sodium channel gene SCN4A. Nevertheless, no muta-tions in SCN4A were identi®ed in this patient. The func