title: Mutation analysis in exons 22 and 24 of SCN4A gene in Iranian patients with non-dystrophic myotonia.
abstract: BACKGROUND
  Non-dystrophic myotonias are a heterogeneous set of skeletal, muscular channelopathies, which have been associated with point mutations within sodium channel α-subunit (SCN4A) gene. Because exons 22 and 24 of SCN4A gene are recognized as hot spots for this disease, the purpose of the study is to identify mutation in exons 22 and 24 of SCN4A gene in Iranian non-dystrophic myotonias patients.
  
  
  METHODS
  In this study, 28 Iranian patients with non-dystrophic myotonia analyzed for the mutation scanning in exons 22 and 24 of SCN4A gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing.
  
  
  RESULTS
  We found 29073G>C substitution in SCN4A gene in one case and 31506A>G substitution in seven cases. The 29073G>C substitution causes a missense mutation G1306A, located in the conserved cytoplasmic loop connecting repeat III and IV of the SCN4A channel but, 31506A>G substitution do not alter amino acid in SCN4A protein.
  
  
  CONCLUSIONS
  G1306A residue is located in functionally important protein region. In "hinged-lid model" for Na(+) channel inactivation in which glycines(1306) act as the hinge of the lid occluding the channel pore. Mutation in this region slowed fast inactivation. Therefore, it might be a pathogenic mutation. The causal relationship of this mutation with the disease is an object for further discussion.
authors.affiliation: Department of Biology, School of Science, Yazd University, Yazd, Iran.
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Heidari
authors.affiliation: Department of Biology, School of Science, Yazd University, Yazd, Iran.
authors.forename: Mehri
authors.initials: M
authors.lastname: Khatami
authors.affiliation: Department of Neurology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Nafissi
authors.affiliation: Department of Biology, School of Science, Yazd University, Yazd, Iran.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Hesami-Zokai
authors.affiliation: Department of Biology, School of Science, Yazd University, Yazd, Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Khorrami
keywords: Mutation; Nondystrophic Myotonia; Polymerase Chain Reaction-Single Strand Conformational Polymorphism; SCN4A