title: Heterozygous CLCN1 mutations can modulate phenotype in sodium channel myotonia.
abstract: Nondystrophic myotonias are characterized by muscle stiffness triggered by voluntary movement. They are caused by mutations in either the CLCN1 gene in myotonia congenita or in the SCN4A gene in paramyotonia congenita and sodium channel myotonias. Clinical and electrophysiological phenotypes of these disorders have been well described. No concomitant mutations in both genes have been reported yet. We report five patients from three families showing myotonia with both chloride and sodium channel mutations. Their clinical and electrophysiological phenotypes did not fit with the phenotype known to be associated with the mutation initially found in SCN4A gene, which led us to screen and find an additional mutation in CLCN1 gene. Our electrophysiological and clinical observations suggest that heterozygous CLCN1 mutations can modify the clinical and electrophysiological expression of SCN4A mutation.
authors.affiliation: CHU Saint-Etienne, Hôpital Nord, Department of Neurology, Saint-Etienne F-42055, France; Rhône-Alpes Reference Center for Rare Neuromuscular Diseases, Saint-Etienne F-42055, France. Electronic address: alain.furby@chu-st-etienne.fr.
authors.forename: A
authors.initials: A
authors.lastname: Furby
authors.affiliation: Assistance Publique-Hôpitaux de Paris, National Reference Center for Neuromuscular Channelopathies, Hôpital Pitié-Salpêtrière, Paris 75013, France.
authors.forename: S
authors.initials: S
authors.lastname: Vicart
authors.affiliation: CHU Saint-Etienne, Hôpital Nord, Department of Neurology, Saint-Etienne F-42055, France; Rhône-Alpes Reference Center for Rare Neuromuscular Diseases, Saint-Etienne F-42055, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Camdessanché
authors.affiliation: Assistance Publique-Hôpitaux de Paris, National Reference Center for Neuromuscular Channelopathies, Hôpital Pitié-Salpêtrière, Paris 75013, France; Université Pierre et Marie Curie-Paris VI, Department of Physiology, 75005 Paris, France; CNRS-INSERM-UPMC UMR 1127-7225, Institut Cerveau Moelle, Hôpital Pitié-Salpêtrière, Paris 75013, France.
authors.forename: E
authors.initials: E
authors.lastname: Fournier
authors.affiliation: Rhône-Alpes Reference Center for Rare Neuromuscular Diseases, Saint-Etienne F-42055, France; CHU Saint-Etienne, Hôpital Bellevue, Department of Paediatric Physical Medicine and Rehabilitation, Saint-Etienne F-42055, France.
authors.forename: S
authors.initials: S
authors.lastname: Chabrier
authors.affiliation: UMR Inserm U930, Université François Rabelais de Tours. CHRU de Tours, Service "Neuropédiatrie et Handicaps", Tours 37044, France.
authors.forename: E
authors.initials: E
authors.lastname: Lagrue
authors.affiliation: Rhône-Alpes Reference Center for Rare Neuromuscular Diseases, Saint-Etienne F-42055, France; CHU Saint-Etienne, Hôpital Nord, Paediatric Intensive Care Unit, Saint-Etienne F-42055, France.
authors.forename: C
authors.initials: C
authors.lastname: Paricio
authors.affiliation: Assistance Publique-Hôpitaux de Paris, National Reference Center for Neuromuscular Channelopathies, Hôpital Pitié-Salpêtrière, Paris 75013, France; CNRS-INSERM-UPMC UMR 1127-7225, Institut Cerveau Moelle, Hôpital Pitié-Salpêtrière, Paris 75013, France; Assistance Publique-Hôpitaux de Paris, Service de Biochimie Métabolique, Centre de Génétique, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Paris 75013, France.
authors.forename: P
authors.initials: P
authors.lastname: Blondy
authors.affiliation: Rhône-Alpes Reference Center for Rare Neuromuscular Diseases, Saint-Etienne F-42055, France; CHU Saint-Etienne, Hôpital Nord, Department of Genetics, Saint-Etienne F-42055, France.
authors.forename: R
authors.initials: R
authors.lastname: Touraine
authors.affiliation: Assistance Publique-Hôpitaux de Paris, National Reference Center for Neuromuscular Channelopathies, Hôpital Pitié-Salpêtrière, Paris 75013, France; CNRS-INSERM-UPMC UMR 1127-7225, Institut Cerveau Moelle, Hôpital Pitié-Salpêtrière, Paris 75013, France; Assistance Publique-Hôpitaux de Paris, Service de Biochimie Métabolique, Centre de Génétique, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Paris 75013, France.
authors.forename: D
authors.initials: D
authors.lastname: Sternberg
authors.affiliation: Assistance Publique-Hôpitaux de Paris, National Reference Center for Neuromuscular Channelopathies, Hôpital Pitié-Salpêtrière, Paris 75013, France; CNRS-INSERM-UPMC UMR 1127-7225, Institut Cerveau Moelle, Hôpital Pitié-Salpêtrière, Paris 75013, France.
authors.forename: B
authors.initials: B
authors.lastname: Fontaine
mesh_terms: D000293:Adolescent; D000328:Adult; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004594:Electrophysiology; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D009224:Myotonia Congenita / Q000235:genetics*; D010641:Phenotype
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels
keywords: CLCN1; Electromyography; Myotonia; Myotonia congenita; Nondystrophic myotonia; Paramyotonia congenita; SCN4A; Sodium channel myotonia