Congenital Myotonia Caused by Mutations in the CIC-1 Chloride Channel Gene

Czech version

Authors: S. Voháňka ^1,2; J. Bednařík ^1,2; D. Páclová ³; J. Sedláčková ³; L. Fajkusová ³
Authors‘ workplace: Neuromuskulární centrum, Neurologická klinika LF MU a FN Brno ¹; CEITEC (Středoevropský technologický institut), MU, Brno ²; Centrum molekulární biologie a genové terapie FN Brno ³
Published in: Cesk Slov Neurol N 2011; 74/107(4): 467-470
Category: Short Communication

Overview

Congenital myotonia is caused by mutations in the CLCN1 chloride channel gene. It can be inherited as either an autosomal dominant (Thomsen’s myotonia) or a recessive (Becker’s myotonia) trait. During 2008–2010, mutations in the chloride channel were found in 7 patients with myotonia, making it the third most frequent cause of myotonia in our records (54 patients with type 2 myotonic dystrophy, 18 with type 1 myotonic dystrophy, and 4 suffering from mutations in the sodium channel). All persons revealed hypertrophic muscles, worsening in cold was found in six cases, and no patients have post-exercise weakness. The semi-dominant mutation p.Arg894X was found most frequently: 5 times among a possible 13 mutations. The recessive mutation p.Pro480HisfsX24 was disclosed three times and p.Phe413Cys twice. All the cases but one are sporadic, thus the majority of patients in our population have Becker´s form of myotonia congenita.

Key words:
myotonia congenita – CLCN1 – channelopathy

Sources

1. Mindell JA, Maduke M, Miller C, Grigorieff N. Projection structure of a CIC-type chloride channel at 6.5-angstrom resolution. Nature 2001; 409(6817): 219–223.

2. Estevez R, Schroeder BC, Accardi A, Jentsch TJ, Pusch M. Conservation of chloride channel structure revealed by an inhibitor binding site in CIC-1. Neuron 2003; 38(1): 47–59.

3. Wu FF, Ryan A, Devaney J, Warnstedt M, Korade--Mirnics Z, Poser B et al. Novel CLCN1 mutations with unique clinical and electrophysiological consequences. Brain 2002; 125(11): 2392–2407.

4. Thomsen J. Töniche Krämpfe in willkürlich beweglichen Muskeln in Folge von ererbter psychisscher. Arch Psychiatrie Nervenkranheiten 1876; 6: 702–718.

5. Becker PE. Zür frage der heterogenit der erblichen myotonien. Nervenarzt 1957; 28(10): 455–460.

6. Fialho D, Schorge S, Pucovska U, Davies NP, Labrum R, Haworth A et al. Chloride channel myotonia: exon 8 hot-spot for dominant-negative interactions. Brain 2007; 130(12): 3265–3274.

7. Mailander V, Heine R, Deymeer F, Lehmann-Horn F. Novel muscle chloride channel mutations and thein effects on heterozygous carriers. Am J Hum Genet 1996; 58(2): 317–324.

8. Plassart-Schiess E, Gervais A, Eymard B, Lagueny A, Pouget J, Warter JM et al. Novel muscle chloride channel (CLCN1) mutations in myotonia congenita with various modes of inheritance including incomplete dominance and penetrance. Neurology 1998; 50(4): 1176–1179.

9. Dunø M, Colding-Jørgensen E, Grunnet M, Jespersen T, Vissing J, Schwartz M. Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype. Eur J Hum Genet 2004; 12(9): 738–743.

10. Sun C, Tranebjaerg L, Torbergsen T, Holmgren G, van Ghelue M. Spectrum of CLCN1 mutations in patients with myotonia congenita in Northern Scandinavia. Eur J Hum Genet 2001; 9(12): 903–909.

11. Nagamitsu S, Matsuura T, Khajavi M, Armstrong R, Gooch C, Harati Y et al. A “dystrophic” variant of autosomal recessive myotonia congenita caused by novel mutations in the CLCN1 gene. Neurology 2000; 55(11): 1697–1703.

12. Trip J, Drost G, van Engelen BG, Faber CG. Drug treatment for myotonia. Cochrane Database Syst Rev 2006; 1: CD004762.

13. Colding-Jørgensen E. Phenotypic variability in myotonia congenita. Muscle Nerve 2005; 32(1): 19–34.