title: Severe phenotypes of paralysis periodica paramyotonia are associated with the Met1592Val mutation in the voltage-gated sodium channel gene (SCN4A) in a Chinese family.
abstract: Paralysis periodica paramyotonia (PPP) is caused by mutation of the adult skeletal muscle sodium channel gene's alpha (α)-subunit (SCN4A). Here, we report four generations of a Chinese family affected by a remarkably severe form of PPP with progressive myopathy. Routine electromyograms (EMG) showed myotonic discharge and after a long exercise test, compound motor action potential amplitudes were markedly decreased by 40-55%. Muscle biopsy revealed obvious vacuolar changes. Moreover, genetic analysis revealed the Met1592Val mutation in the α-subunit, SCN4A. The patients showed a striking clinical and electrophysiological improvement during treatment with acetazolamide. Thus, our findings showed that mutation of Met1592Val in the SCN4A gene is associated with aggressive development of PPP characterized by severe vacuolar myopathy.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, China Medical University, 155 North Nanjing Street, Heping District, Shengyang 110001, Liaoning, China. fengyu_1976@163.com
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.forename: Xinping
authors.initials: X
authors.lastname: Ji
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Sun
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Chaodong
authors.initials: C
authors.lastname: Zhang
mesh_terms: D002681:China; D004252:DNA Mutational Analysis; D004576:Electromyography; D005192:Family Health; D020022:Genetic Predisposition to Disease; D006801:Humans; D008715:Methionine / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D020967:Myotonic Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D062553:NAV1.4 Voltage-Gated Sodium Channel; D009431:Neural Conduction / Q000502:physiology; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*; D014633:Valine / Q000235:genetics*
chemical_list: D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels; D008715:Methionine; D014633:Valine