title: Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.
abstract: Mutations in the skeletal muscle sodium channel gene (SCN4A) have been described in paramyotonia congenita (PMC) and hyperkalaemic periodic paralysis (HPP). We have found two mutations in SCN4A which affect regions of the sodium channel not previously associated with a disease phenotype. Furthermore, affected family members display an unusual mixture of clinical features reminiscent of PMC, HPP and of a third disorder, myotonia congenita (MC). The highly variable individual expression of these symptoms, including in some cases apparent non-penetrance, implies the existence of modifying factors. Mutations in SCN4A can produce a broad range of phenotypes in muscle diseases characterized by episodic abnormalities of membrane excitability.
authors.affiliation: Molecular Neurogenetics Laboratory, Massachusetts General Hospital, Boston.
authors.forename: A I
authors.initials: AI
authors.lastname: McClatchey
authors.forename: D
authors.initials: D
authors.lastname: McKenna-Yasek
authors.forename: D
authors.initials: D
authors.lastname: Cros
authors.forename: H G
authors.initials: HG
authors.lastname: Worthen
authors.forename: R W
authors.initials: RW
authors.lastname: Kuncl
authors.forename: S M
authors.initials: SM
authors.lastname: DeSilva
authors.forename: D R
authors.initials: DR
authors.lastname: Cornblath
authors.forename: J F
authors.initials: JF
authors.lastname: Gusella
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
mesh_terms: D000328:Adult; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism; D009224:Myotonia Congenita / Q000235:genetics / Q000378:metabolism; D010245:Paralyses, Familial Periodic / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D015222:Sodium Channels; D004247:DNA