CLCN1

Summary

Gene Symbol: CLCN1
Description: chloride voltage-gated channel 1
Alias: CLC1, chloride channel protein 1, chloride channel 1, skeletal muscle, chloride channel protein, skeletal muscle, chloride channel, voltage-sensitive 1, clC-1
Species: human
Products:     CLCN1

Top Publications

  1. Heine R, George A, Pika U, Deymeer F, Rudel R, Lehmann Horn F. Proof of a non-functional muscle chloride channel in recessive myotonia congenita (Becker) by detection of a 4 base pair deletion. Hum Mol Genet. 1994;3:1123-8 pubmed
  2. Koch M, Ricker K, Otto M, Wolf F, Zoll B, Lorenz C, et al. Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker). J Med Genet. 1993;30:914-7 pubmed
    ..Recently, we showed complete linkage of the disorder GM to the gene (CLCN1) coding for the skeletal muscle chloride channel CLC-1 and the TCRB gene on chromosome 7 in German families...
  3. Bennetts B, Rychkov G, Ng H, Morton C, Stapleton D, Parker M, et al. Cytoplasmic ATP-sensing domains regulate gating of skeletal muscle ClC-1 chloride channels. J Biol Chem. 2005;280:32452-8 pubmed
    ..This defines a function for these domains as gating-modulatory domains sensitive to intracellular ligands, such as nucleotides, a function that is likely to be conserved in other ClC proteins. ..
  4. Brugnoni R, Kapetis D, Imbrici P, Pessia M, Canioni E, Colleoni L, et al. A large cohort of myotonia congenita probands: novel mutations and a high-frequency mutation region in exons 4 and 5 of the CLCN1 gene. J Hum Genet. 2013;58:581-7 pubmed publisher
    ..after forceful contraction (myotonia) and caused by mutations in the chloride channel voltage-sensitive 1 (CLCN1) gene, encoding the voltage-gated chloride channel of skeletal muscle (ClC-1)...
  5. Jou S, Chang L, Pan H, Chen P, Hsiao K. Novel CLCN1 mutations in Taiwanese patients with myotonia congenita. J Neurol. 2004;251:666-70 pubmed
    We have performed genetic screening on the skeletal muscle chloride channel gene (CLCN1) in Taiwanese population. A total of four patients with myotonia congenita (MC) together with 106 normal individuals were examined...
  6. Tang C, Chen T. Physiology and pathophysiology of CLC-1: mechanisms of a chloride channel disease, myotonia. J Biomed Biotechnol. 2011;2011:685328 pubmed publisher
  7. 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;55:1697-703 pubmed
    ..To identify the disease-causing mutation and its molecular consequence for a clinically distinct type of myotonic myopathy...
  8. Papponen H, Nissinen M, Kaisto T, Myllyla V, Myllyla R, Metsikkö K. F413C and A531V but not R894X myotonia congenita mutations cause defective endoplasmic reticulum export of the muscle-specific chloride channel CLC-1. Muscle Nerve. 2008;37:317-25 pubmed
    ..The C-terminal nonsense mutant (R894X), however, was normally transported to the Golgi elements in the myofibers. Defective export or reduced stability of the mutated proteins may thus be reasons for the myotonic symptoms. ..
  9. Bennetts B, Parker M, Cromer B. Inhibition of skeletal muscle ClC-1 chloride channels by low intracellular pH and ATP. J Biol Chem. 2007;282:32780-91 pubmed
    ..The modulation of ClC-1 by ATP is a key component of this molecular mechanism. ..

More Information

Publications74

  1. Zhang X, Li Y, Yu W, Chen T. Roles of K149, G352, and H401 in the channel functions of ClC-0: testing the predictions from theoretical calculations. J Gen Physiol. 2006;127:435-47 pubmed
    ..The control of the accessibility to charged MTS reagents and the regulation of the anion permeation support the idea that K149 exerts an electrostatic effect on the channel function, confirming the prediction from computational studies. ..
  2. Cardani R, Giagnacovo M, Botta A, Rinaldi F, Morgante A, Udd B, et al. Co-segregation of DM2 with a recessive CLCN1 mutation in juvenile onset of myotonic dystrophy type 2. J Neurol. 2012;259:2090-9 pubmed publisher
    ..Splicing analysis of the INSR, CLCN1 and MBNL1 genes in muscle tissue demonstrates that the level of aberrant splicing isoforms was lower in the ..
  3. Tseng P, Bennetts B, Chen T. Cytoplasmic ATP inhibition of CLC-1 is enhanced by low pH. J Gen Physiol. 2007;130:217-21 pubmed
    ..Here we show that in the presence of physiological concentrations of ATP, reduction of the intracellular pH indeed inhibits the expressed CLC-1, mostly by decreasing the open probability of the common gate of the channel. ..
  4. Pusch M. Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Hum Mutat. 2002;19:423-34 pubmed
    ..in the genes coding for the skeletal muscle sodium channel (SCN5A) or the skeletal muscle chloride channel (CLCN1) with similar phenotypes...
  5. 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;9:903-9 pubmed
    ..muscle stiffness) and muscular hypertrophy, and are caused by mutations in the muscle chloride channel gene, CLCN1. At least 50 different CLCN1 mutations have been described worldwide, but in many studies only about half of the ..
  6. Mailänder V, Heine R, Deymeer F, Lehmann Horn F. Novel muscle chloride channel mutations and their effects on heterozygous carriers. Am J Hum Genet. 1996;58:317-24 pubmed
    Mutations within CLCN1, the gene encoding the major skeletal muscle chloride channel, cause either dominant Thomsen disease or recessive Becker-type myotonia, which are sometimes difficult to discriminate, because of reduced penetrance ..
  7. Gao F, Ma F, Yuan Z, Yang C, Li H, Xia Z, et al. Novel chloride channel gene mutations in two unrelated Chinese families with myotonia congenita. Neurol India. 2010;58:743-6 pubmed publisher
    Myotonia congenita (MC) is a genetic disease characterized by mutations in the muscle chloride channel gene (CLCN1). To date, approximately 130 different mutations on the CLCN1 gene have been identified...
  8. Pusch M, Steinmeyer K, Koch M, Jentsch T. Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel. Neuron. 1995;15:1455-63 pubmed
    ..Remarkably, a human mutation affecting an adjacent residue (E291K) is fully recessive. Large shifts in the voltage dependence of gating may be common to many mutations in dominant myotonia congenita...
  9. Macias M, Teijido O, Zifarelli G, Martin P, Ramirez Espain X, Zorzano A, et al. Myotonia-related mutations in the distal C-terminus of ClC-1 and ClC-0 chloride channels affect the structure of a poly-proline helix. Biochem J. 2007;403:79-87 pubmed
    ..We provide the first experimental investigation of structural changes resulting from myotonia-causing mutations...
  10. Ma L, Rychkov G, Hughes B, Bretag A. Analysis of carboxyl tail function in the skeletal muscle Cl- channel hClC-1. Biochem J. 2008;413:61-9 pubmed publisher
  11. Fahlke C, Beck C, George A. A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel. Proc Natl Acad Sci U S A. 1997;94:2729-34 pubmed
    ..congenita is an inherited disorder of skeletal muscle caused by mutations in a voltage-gated Cl- channel gene (CLCN1, 7q35)...
  12. Trip J, Drost G, Ginjaar H, Nieman F, van der Kooi A, de Visser M, et al. Redefining the clinical phenotypes of non-dystrophic myotonic syndromes. J Neurol Neurosurg Psychiatry. 2009;80:647-52 pubmed publisher
    ..This study redefined the phenotypical characteristics of NDM in both ClCh and NaCh. The clinical guidelines proposed may help clinicians working in outpatient clinics to perform a focused genetic analysis of either CLCN1 or SCN4A.
  13. Moon I, Kim H, Shin J, Park Y, Park K, Shin Y, et al. Novel CLCN1 mutations and clinical features of Korean patients with myotonia congenita. J Korean Med Sci. 2009;24:1038-44 pubmed publisher
    Myotonia congenita (MC) is a form of nondystrophic myotonia caused by a mutation of CLCN1, which encodes human skeletal muscle chloride channel (CLC-1)...
  14. Weinberger S, Wojciechowski D, Sternberg D, Lehmann Horn F, Jurkat Rott K, Becher T, et al. Disease-causing mutations C277R and C277Y modify gating of human ClC-1 chloride channels in myotonia congenita. J Physiol. 2012;590:3449-64 pubmed publisher
    Myotonia congenita is a genetic condition that is caused by mutations in the muscle chloride channel gene CLCN1 and characterized by delayed muscle relaxation and muscle stiffness...
  15. Charlet B N, Savkur R, Singh G, Philips A, Grice E, Cooper T. Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol Cell. 2002;10:45-53 pubmed
    ..We propose that disruption of alternative splicing regulation causes a predominant pathological feature of DM1. ..
  16. Mankodi A, Takahashi M, Jiang H, Beck C, Bowers W, Moxley R, et al. Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell. 2002;10:35-44 pubmed
    ..We propose that a transdominant effect of mutant RNA on RNA processing leads to chloride channelopathy and membrane hyperexcitability in DM. ..
  17. Steinmeyer K, Lorenz C, Pusch M, Koch M, Jentsch T. Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen). EMBO J. 1994;13:737-43 pubmed
    ..Analysis of both mutants shows independently that ClC-1 functions as a homooligomer with most likely four subunits...
  18. Koch M, Steinmeyer K, Lorenz C, Ricker K, Wolf F, Otto M, et al. The skeletal muscle chloride channel in dominant and recessive human myotonia. Science. 1992;257:797-800 pubmed
    ..This suggests that different mutations in CLC-1 may cause dominant or recessive myotonia...
  19. Richman D, Yu Y, Lee T, Tseng P, Yu W, Maselli R, et al. Dominantly inherited myotonia congenita resulting from a mutation that increases open probability of the muscle chloride channel CLC-1. Neuromolecular Med. 2012;14:328-37 pubmed publisher
    ..ZNF9 genes for myotonic muscular dystrophy types I and II was normal, whereas sequencing of CLC-1 encoding gene, CLCN1, identified a single heterozygous missense mutation, G233S...
  20. Trip J, Drost G, Verbove D, van der Kooi A, Kuks J, Notermans N, et al. In tandem analysis of CLCN1 and SCN4A greatly enhances mutation detection in families with non-dystrophic myotonia. Eur J Hum Genet. 2008;16:921-9 pubmed publisher
    Non-dystrophic myotonias (NDMs) are caused by mutations in CLCN1 or SCN4A. The purpose of the present study was to optimize the genetic characterization of NDM in The Netherlands by analysing CLCN1 and SCN4A in tandem...
  21. Shalata A, Furman H, Adir V, Adir N, Hujeirat Y, Shalev S, et al. Myotonia congenita in a large consanguineous Arab family: insight into the clinical spectrum of carriers and double heterozygotes of a novel mutation in the chloride channel CLCN1 gene. Muscle Nerve. 2010;41:464-9 pubmed publisher
    ..Genomic DNA was extracted from peripheral blood samples for sequencing the exons of the CLCN1 gene...
  22. Sun C, Van Ghelue M, Tranebjærg L, Thyssen F, Nilssen Ø, Torbergsen T. Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene. Clin Genet. 2011;80:574-80 pubmed publisher
    ..are identified to be involved in myotonia: the muscle voltage-gated sodium and chloride channel genes SCN4A and CLCN1, the myotonic dystrophy protein kinase (DMPK) gene, and the CCHC-type zinc finger, nucleic acid binding protein ..
  23. Ulzi G, Lecchi M, Sansone V, Redaelli E, Corti E, Saccomanno D, et al. Myotonia congenita: novel mutations in CLCN1 gene and functional characterizations in Italian patients. J Neurol Sci. 2012;318:65-71 pubmed publisher
    ..and variable degrees of permanent muscle weakness, abnormal currents linked to the chloride channel gene (CLCN1) encoding the chloride channel on skeletal muscle membrane. We describe 12 novel mutations: c.1606G>C (p...
  24. Zhang J, Bendahhou S, Sanguinetti M, Ptacek L. Functional consequences of chloride channel gene (CLCN1) mutations causing myotonia congenita. Neurology. 2000;54:937-42 pubmed
    To determine the functional consequences of missense mutations within the skeletal muscle chloride channel gene CLCN1 that cause myotonia congenita.
  25. Kubisch C, Schmidt Rose T, Fontaine B, Bretag A, Jentsch T. ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependence. Hum Mol Genet. 1998;7:1753-60 pubmed
    ..These complex interactions correlate clinically with various inheritance patterns, ranging from autosomal dominant with various degrees of penetrance to autosomal recessive...
  26. Colding Jørgensen E. Phenotypic variability in myotonia congenita. Muscle Nerve. 2005;32:19-34 pubmed
    ..It is caused by mutations in the skeletal muscle chloride channel gene CLCN1 on chromosome 7...
  27. Estévez R, Schroeder B, Accardi A, Jentsch T, Pusch M. Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1. Neuron. 2003;38:47-59 pubmed
    ..Mutations in presumably Cl--coordinating residues yield additional insights into the structure and function of ClC-1. Our work shows that the structure of bacterial CLCs can be extrapolated with fidelity to mammalian Cl- channels. ..
  28. Colding Jørgensen E, Dunø M, Schwartz M, Vissing J. Decrement of compound muscle action potential is related to mutation type in myotonia congenita. Muscle Nerve. 2003;27:449-55 pubmed
    ..It was the purpose of the present study to elucidate the relation between decrement and CLCN1 mutation type in myotonia congenita...
  29. Meyer Kleine C, Steinmeyer K, Ricker K, Jentsch T, Koch M. Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia. Am J Hum Genet. 1995;57:1325-34 pubmed
    ..Recently, these two phenotypes have been associated with mutations in the major muscle chloride channel gene CLCN1 on human chromosome 7q35...
  30. Lee T, Zhang X, Chuang C, Chen J, Chen Y, Chen S, et al. Myotonia congenita mutation enhances the degradation of human CLC-1 chloride channels. PLoS ONE. 2013;8:e55930 pubmed publisher
    ..These results demonstrate that the molecular pathophysiology of A531V does not involve anomalous channel gating, but rather a disruption of the balance between the synthesis and degradation of the CLC-1 channel protein. ..
  31. George A, Crackower M, Abdalla J, Hudson A, Ebers G. Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita). Nat Genet. 1993;3:305-10 pubmed
    ..This glycine residue is conserved in all known members of this class of chloride channel proteins. These findings establish HUMCLC as the Thomsen's disease gene...
  32. Cederholm J, Rychkov G, Bagley C, Bretag A. Inter-subunit communication and fast gate integrity are important for common gating in hClC-1. Int J Biochem Cell Biol. 2010;42:1182-8 pubmed publisher
    ..Common gating is practically eliminated in V292L and open probability is shifted to more depolarised potentials in A272V, S289L and T293L mainly by altering the voltage dependence of common gating. ..
  33. George A, Sloan Brown K, Fenichel G, Mitchell G, Spiegel R, Pascuzzi R. Nonsense and missense mutations of the muscle chloride channel gene in patients with myotonia congenita. Hum Mol Genet. 1994;3:2071-2 pubmed
  34. Lehmann Horn F, Mailänder V, Heine R, George A. Myotonia levior is a chloride channel disorder. Hum Mol Genet. 1995;4:1397-402 pubmed
    ..Dominant myotonia congenita (Thomsen's disease) is linked to CLCN1, the gene encoding the major muscle chloride channel, localized on chromosome 7q35...
  35. Suominen T, Schoser B, Raheem O, Auvinen S, Walter M, Krahe R, et al. High frequency of co-segregating CLCN1 mutations among myotonic dystrophy type 2 patients from Finland and Germany. J Neurol. 2008;255:1731-6 pubmed publisher
    Based on previous reports the frequency of co-segregating recessive chloride channel (CLCN1) mutations in families with myotonic dystrophy type 2 (DM2) was suspected to be increased...
  36. Mazón M, Barros F, de la Pena P, Quesada J, Escudero A, Cobo A, et al. Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene. Neuromuscul Disord. 2012;22:231-43 pubmed publisher
    Myotonia congenita is an inherited muscle disorder caused by mutations in the CLCN1 gene, a voltage-gated chloride channel of skeletal muscle...
  37. Berg J, Jiang H, Thornton C, Cannon S. Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current. Neurology. 2004;63:2371-5 pubmed
    ..These data show that the aberrantly spliced chloride channel message exerts a dominant negative effect that may contribute to the development of myotonia. ..
  38. Lorenz C, Meyer Kleine C, Steinmeyer K, Koch M, Jentsch T. Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia. Hum Mol Genet. 1994;3:941-6 pubmed
    ..Mutations in the gene encoding this chloride channel (CLCN1) are responsible for both human purely myotonic disorders, autosomal recessive generalized myotonia (Becker's ..
  39. Mitchell C, Bertorini T. Diffusely increased insertional activity: "EMG disease" or asymptomatic myotonia congenita? A report of 2 cases. Arch Phys Med Rehabil. 2007;88:1212-3 pubmed
    ..We describe 2 patients with diffusely increased insertional activity on electromyography who had mutations of the CLCN1 gene associated with myotonia congenita. Neither patient had symptoms or reproducible signs of this disorder...
  40. Thomas J, Tarleton J, Baker S. Recessive CLCN1 mutation presenting as Thomsen disease. Muscle Nerve. 2008;38:1515-1517 pubmed publisher
    ..Investigations not only confirmed Thomsen myotonia, but also led to the identification of a previously reported heterozygous Becker mutation in both the proband and his mother...
  41. Peng Y, Huang J, Wu H, Hsieh H, Wu C, Chen S, et al. Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90?. Sci Rep. 2016;6:32444 pubmed publisher
    ..Our data are consistent with the idea that FKBP8 and Hsp90? play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation. ..
  42. Isobe M, Erikson J, Emanuel B, Nowell P, Croce C. Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells. Science. 1985;228:580-2 pubmed
    ..This chromosome region in T cells is unusually prone to develop breaks in vivo, perhaps reflecting instability generated by somatic rearrangement of T-cell receptor genes during normal differentiation in this cell lineage. ..
  43. Sasaki R, Takahashi M, Kokunai Y, Hirayama M, Ibi T, Tomimoto H, et al. [Compound heterozygous mutations in the muscle chloride channel gene (CLCN1) in a Japanese family with Thomsen's disease]. Rinsho Shinkeigaku. 2013;53:316-9 pubmed
    ..one (Becker's disease) are caused by mutations in the skeletal muscle voltage-gated chloride channel gene (CLCN1). Clinical manifestation of the diseases ranges from minimum to severely disabling myotonia...
  44. Vásquez Soto B, Manríquez N, Cruz Amaya M, Zouhar J, Raikhel N, Norambuena L. Sortin2 enhances endocytic trafficking towards the vacuole in Saccharomyces cerevisiae. Biol Res. 2015;48:39 pubmed publisher
    ..mutants that do not secrete CPY when grown at Sortin2 condition where the parental strain does: met18, sla1, clc1, dfg10, dpl1 and yjl175w...
  45. Maggi L, Ravaglia S, Farinato A, Brugnoni R, Altamura C, Imbrici P, et al. Coexistence of CLCN1 and SCN4A mutations in one family suffering from myotonia. Neurogenetics. 2017;18:219-225 pubmed publisher
    ..findings in a girl and her father concomitantly harbouring single heterozygous mutations in SCN4A and CLCN1 genes. Functional characterization of N1297S hNav1.4 mutant was performed by patch clamp...
  46. Wu W, Rychkov G, Hughes B, Bretag A. Functional complementation of truncated human skeletal-muscle chloride channel (hClC-1) using carboxyl tail fragments. Biochem J. 2006;395:89-97 pubmed
    ..We have found that just 26 amino acids from Leu863 to Arg888 are necessary since channel function is restored by co-expressing this peptide with the otherwise inactive truncation, G721X. ..
  47. McKay O, Krishnan A, Davis M, Kiernan M. Activity-induced weakness in recessive myotonia congenita with a novel (696+1G>A) mutation. Clin Neurophysiol. 2006;117:2064-8 pubmed
    ..Nerve excitability studies were performed on a 35-year-old male with RMC due to a novel 696+1G>A CLCN1 mutation...
  48. Pedersen T, Riisager A, de Paoli F, Chen T, Nielsen O. Role of physiological ClC-1 Cl- ion channel regulation for the excitability and function of working skeletal muscle. J Gen Physiol. 2016;147:291-308 pubmed publisher
    ..with skeletal muscle hyperexcitability in myotonia congenita, which arises from loss-of-function mutations in the CLCN1 gene...
  49. Chen Y, Peng Y, Hu M, Huang J, Chien Y, Wu J, et al. The Cullin 4A/B-DDB1-Cereblon E3 Ubiquitin Ligase Complex Mediates the Degradation of CLC-1 Chloride Channels. Sci Rep. 2015;5:10667 pubmed publisher
    ..Our data are consistent with the idea that the CUL4A/B-DDB1-CRBN complex catalyses the polyubiquitination and thus controls the degradation of CLC-1 channels. ..
  50. Chang T, Kuo H, Hsiao K, Huang C. Phenotypic variability of autosomal dominant myotonia congenita in a Taiwanese family with muscle chloride channel (CLCN1) mutation. Acta Neurol Taiwan. 2007;16:214-20 pubmed
    Myotonia congenita (MC), whether inherited in autosomal dominant or recessive form, is caused by mutation of CLCN1 on chromosome 7 and associated with impaired skeletal muscle relaxation after contraction...
  51. Ebralidze A, Wang Y, Petkova V, Ebralidse K, Junghans R. RNA leaching of transcription factors disrupts transcription in myotonic dystrophy. Science. 2004;303:383-7 pubmed
    ..Transcription factor leaching from chromatin by mutant RNA provides a potentially unifying pathomechanistic explanation for this disease. ..
  52. Lakraj A, Miller G, Vortmeyer A, Khokhar B, Nowak R, Dicapua D. Novel mutations in the CLCN1 gene of myotonia congenita: 2 case reports. Yale J Biol Med. 2013;86:101-6 pubmed
    Myotonia Congenita is an inherited myotonia that is due to a mutation in the skeletal muscle chloride channel CLCN1. These mutations lead to reduced sarcolemmal chloride conductance, causing delayed muscle relaxation that is evident as ..
  53. Ronstedt K, Sternberg D, Detro Dassen S, Gramkow T, Begemann B, Becher T, et al. Impaired surface membrane insertion of homo- and heterodimeric human muscle chloride channels carrying amino-terminal myotonia-causing mutations. Sci Rep. 2015;5:15382 pubmed publisher
    Mutations in the muscle chloride channel gene (CLCN1) cause myotonia congenita, an inherited condition characterized by muscle stiffness upon sudden forceful movement...
  54. Tsujino A, Kaibara M, Hayashi H, Eguchi H, Nakayama S, Sato K, et al. A CLCN1 mutation in dominant myotonia congenita impairs the increment of chloride conductance during repetitive depolarization. Neurosci Lett. 2011;494:155-60 pubmed publisher
    Myotonia congenita is caused by mutation of the CLCN1 gene, which encodes the human skeletal muscle chloride channel (ClC-1). The ClC-1 protein is a dimer comprised of two identical subunits each incorporating its own separate pore...
  55. Morales F, Cuenca P, Del Valle G, Vásquez M, Brian R, Sittenfeld M, et al. Clinical and molecular diagnosis of a Costa Rican family with autosomal recessive myotonia congenita (Becker disease) carrying a new mutation in the CLCN1 gene. Rev Biol Trop. 2008;56:1-11 pubmed
    ..clinical diagnosis of a family diagnosed with a myotonic condition many years ago and report a new mutation in the CLCN1 gene...
  56. Lin M, You T, Pan H, Hsiao K. Functional characterization of CLCN1 mutations in Taiwanese patients with myotonia congenita via heterologous expression. Biochem Biophys Res Commun. 2006;351:1043-7 pubmed
    Mutations in the CLCN1 gene frequently associate with myotonia congenita (MC). We have recently reported several CLCN1 mutants in Taiwanese patients...
  57. Skálová D, Zídková J, Vohanka S, Mazanec R, Musova Z, Vondracek P, et al. CLCN1 mutations in Czech patients with myotonia congenita, in silico analysis of novel and known mutations in the human dimeric skeletal muscle chloride channel. PLoS ONE. 2013;8:e82549 pubmed publisher
    Myotonia congenita (MC) is a genetic disease caused by mutations in the skeletal muscle chloride channel gene (CLCN1) encoding the skeletal muscle chloride channel (ClC-1)...
  58. Portaro S, Altamura C, Licata N, Camerino G, Imbrici P, Musumeci O, et al. Clinical, Molecular, and Functional Characterization of CLCN1 Mutations in Three Families with Recessive Myotonia Congenita. Neuromolecular Med. 2015;17:285-96 pubmed publisher
    ..Both recessive (Becker's disease) or dominant (Thomsen's disease) MC are caused by mutations in the CLCN1 gene encoding the voltage-dependent chloride ClC-1 channel, which is quite exclusively expressed in skeletal ..
  59. Lamb F, Clayton G, Liu B, Smith R, Barna T, Schutte B. Expression of CLCN voltage-gated chloride channel genes in human blood vessels. J Mol Cell Cardiol. 1999;31:657-66 pubmed
    ..The CLCN family of voltage-dependent Cl channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence ..
  60. Meng Y, Zhao Z, Shen H, Bing Q, Hu J. Identification of novel mutations of the CLCN1 gene for myotonia congenital in China. Neurol Res. 2016;38:40-4 pubmed publisher
    ..Optimization PCR was used to exclude myotonic dystrophies and the CLCN1 gene was sequenced in patients having clinical and electrophysiological features indicative of MC...
  61. Trivedi J, Bundy B, Statland J, Salajegheh M, Rayan D, Venance S, et al. Non-dystrophic myotonia: prospective study of objective and patient reported outcomes. Brain. 2013;136:2189-200 pubmed publisher
  62. Bernard G, Poulin C, Puymirat J, Sternberg D, Shevell M. Dosage effect of a dominant CLCN1 mutation: a novel syndrome. J Child Neurol. 2008;23:163-6 pubmed publisher
    Multiple mutations in the CLCN1 gene coding for the voltage-gated chloride channel have been documented to cause myotonia congenita...
  63. Kornblum C, Lutterbey G, Czermin B, Reimann J, von Kleist Retzow J, Jurkat Rott K, et al. Whole-body high-field MRI shows no skeletal muscle degeneration in young patients with recessive myotonia congenita. Acta Neurol Scand. 2010;121:131-5 pubmed publisher
    ..We hypothesized that in severe myotonia congenita type Becker muscle stiffness, prolonged transient weakness and muscle hypertrophy might finally result in morphologic skeletal muscle alterations reflected by MRI signal changes...
  64. Kumar K, Ng K, Vandebona H, Davis M, Sue C. A novel CLCN1 mutation (G1652A) causing a mild phenotype of thomsen disease. Muscle Nerve. 2010;41:412-5 pubmed publisher
    ..He was found to have a novel heterozygous G-to-A nucleotide substitution at position 1652 in exon 15 of the CLCN1 gene. Clinicogenetic studies performed on his family revealed that his asymptomatic son also shared the mutation...