Iranian Journal of Neurology 2015. 14(4):190-194.

Mutation analysis in exons 22 and 24 of SCN4A gene in Iranian patients with non-dystrophic myotonia
Mohammad Mehdi Heidari, Mehri Khatami, Shahriar Nafissi, Faezeh Hesami-Zokai, Afshin Khorrami

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.
Conclusion: G1306A residue is located in functionally important protein region. In “hinged-lid model” for Na+ channel inactivation in which glycines1306 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.


Keywords


Nondystrophic Myotonia; Mutation; SCN4A; Polymerase Chain; Reaction Single Strand;Conformational Polymorphism

Full Text:

PDF

References


Heatwole CR, Moxley RT. The nondystrophic myotonias. Neurotherapeutics 2007; 4(2): 238-51.

Lehmann-Horn F, Rudel R. Hereditary nondystrophic myotonias and periodic paralyses. Curr Opin Neurol 1995; 8(5): 402-10.

Emery AE. Population frequencies of inherited neuromuscular diseases--a world survey. Neuromuscul Disord 1991; 1(1):

-29.

Chino N, Noda Y, Oda N. Conduction study in human muscle fibers in situ-a useful technique for diagnosing myopathies. Electroencephalogr Clin Neurophysiol 1984; 58(6): 513-6.

Lee SC, Kim HS, Park YE, Choi YC, Park KH, Kim DS. Clinical Diversity of SCN4A-Mutation-Associated Skeletal Muscle Sodium Channelopathy. J Clin Neurol 2009; 5(4): 186-91.

Stuhmer W, Conti F, Suzuki H, Wang XD, Noda M, Yahagi N, et al. Structural parts involved in activation and inactivation of the sodium channel. Nature 1989; 339(6226): 597-603.

Bendahhou S, Cummins TR, Kwiecinski H, Waxman SG, Ptacek LJ. Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans. J Physiol 1999; 518 (Pt 2): 337-44.

Matthews E, Fialho D, Tan SV, Venance SL, Cannon SC, Sternberg D, et al. The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain 2010; 133(Pt 1): 9-22.

Matthews E, Tan SV, Fialho D, Sweeney MG, Sud R, Haworth A, et al. What causes paramyotonia in the United Kingdom? Common and new SCN4A mutations revealed. Neurology 2008; 70(1): 50-3.

Sambrook J, Russell DW. Molecular Cloning: A Laboratory Manual. New York, NY: Cold Spring Harbor Laboratory; 2001.

Trip J, Drost G, Verbove DJ, van der Kooi AJ, Kuks JB, Notermans NC, 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(8): 921-9.

Lerche H, Heine R, Pika U, George AL,

Mitrovic N, Browatzki M, et al. Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker. J Physiol 1993; 470: 13-22.

McClatchey AI, Van den Bergh P, Pericak-Vance MA, Raskind W, Verellen C, McKenna-Yasek D, et al. Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita. Cell 1992; 68(4): 769-74.

Vicart S, Sternberg D, Fontaine B, Meola G. Human skeletal muscle sodium channelopathies. Neurol Sci 2005; 26(4): 194-202.

West JW, Patton DE, Scheuer T, Wang Y, Goldin AL, Catterall WA. A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation. Proc Natl Acad Sci U S A 1992; 89(22):

-4.

Lehmann-Horn F, Jurkat-Rott K. Voltage-gated ion channels and hereditary disease. Physiol Rev 1999; 79(4): 1317-72.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.