Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019, 163(4):362-365 | DOI: 10.5507/bp.2018.078

Paramyotonia congenita in a Slovak population: Genetic and pedigree analysis of 3 families

Frantisek Cibulcika, Peter Spaleka, Ivan Martinkaa, Jana Zidkovab, Milan Grofikc, Stefan Sivakc, Egon Kurcac
a Department of Neurology, Faculty of Medicine, Slovak Health University, University Hospital Bratislava, Slovak Republic
b Centre of Molecular Biology and Gene Therapy, University Hospital Brno, Czech Republic
c Clinic of Neurology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital Martin, Slovak Republic

Background: Paramyotonia congenita is a non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction. This condition cannot be distinguished on the basis of symptoms and signs alone. It requires consideration of genetics as more than 100 mutations in the CLCN1 gene and at least 20 mutations in the SCN4A gene are associated with the clinical features of the non-dystrophic myotonias. Only a few families with the described features but no genetic testing have been reported in Slovakia. This prompted us to investigate genetic mutations in the SCN4A gene in 3 Slovak families clinically diagnosed with paramyotonia.

Subjects and Methods: Genomic DNA of the family members was extracted from peripheral blood and amplified by polymerase chain reaction. SCN4A variants were screened by Sanger sequencing.

Results: Our results revealed 2 potential disease-causing mutations present in the probands and affected family members - mutations c.3938C > T (p.T1313M) in two families and mutation c.2111C>T (p. T704M) in one family.

Conclusion: Our results may help to identify genetic determinants as well as clarify genotype-phenotype relationships in patients with paramyotonia in Slovakia.

Keywords: paramyotonia, periodic paralysis, genetics

Received: July 23, 2018; Accepted: December 9, 2018; Prepublished online: January 14, 2019; Published: December 11, 2019  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Cibulcik, F., Spalek, P., Martinka, I., Zidkova, J., Grofik, M., Sivak, S., & Kurca, E. (2019). Paramyotonia congenita in a Slovak population: Genetic and pedigree analysis of 3 families. Biomedical papers, 163(4), 362-365. doi: 10.5507/bp.2018.078
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Matthews E, Fialho D, Tan SV, Venance SL, Cannon SC, Sternberg D, Fontaine B, Amato AA, Barohn RJ, Griggs RC, Hanna MG; CINCH Investigators. The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain 2010;133:9-22. Go to original source... Go to PubMed...
    2. George AL, Komisarof J, Kallen RG, Barchi RL. Primary structure of the adult human skeletal voltage-dependent sodium channel. Ann Neurol 1992;31:131-7. Go to original source... Go to PubMed...
    3. Cannon SC, Brown RH Jr, Corey DP. Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels. Biophys J 1993;65:270-88. Go to original source... Go to PubMed...
    4. Nicole S, Fontaine B. Skeletal muscle sodium chanellopaties. Curr Opin Neurol 2015; 28:508-14. Go to original source... Go to PubMed...
    5. Meyer-Kleine C, Steinmeyer K, Ricker K, Jentsh TJ, Koch MC. Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia. Am J Hum Genet 1995;57:1325-34.
    6. Heatwole CR, Statland JM, Logigian EL. The diagnosis and treatment of myotonic disorders. Muscle Nerve 2013;47:632-48. Go to original source... Go to PubMed...
    7. Špalek P, Lisý Ľ, Orolin D, Štofej P. Kongenitálna myotónia Eulenburg. Čs Neurol Neurochir 1980;43/76:203-7.
    8. Lehmann-Horn F, Ruedel R. Non-dystrophic myotonias and periodic paralyses. In: Emery AEH (ed).: Diagnostic Criteria for Neuromuscular Disorders. London: Royal Society of Medicine Press 1997; pp 31-6.
    9. Ptácek LJ, George AL Jr, Griggs RC, Tawil R, Kallen RG, Barchi RL, Robertson, M, Leppert MF. Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell 1991;67:1021-7. Go to original source... Go to PubMed...
    10. Ptacek L. The familial periodic paralyses and nondystrophic myotonias. Am J Med 1998;105:58-70. Go to original source... Go to PubMed...
    11. Noda M, Shimizu S, Tanabe T, Takai T, Kayano T, Ikeda T, Takahashi H, Nakayama H, Kanaoka Y, Minamino N, Kangawa K, Matsuo H, Raftery MA, Hirose T, Inayama S, Hayashida H, Miyata T, Numa S. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature 1984; 312:121-7. Go to original source... Go to PubMed...
    12. Nurputra DK, Nakagawa T, Takeshima Y, Harahap IS, Morikawa S, Sakaeda T, La PS, Matsuo M, Takaoka Y, Nishio H. Paramyotonia congenita: from clinical diagnosis to in silico protein modeling analysis. Pediatr Int 2012;54:602-12. Go to original source... Go to PubMed...
    13. Matthews E, Tan SV, Fialho D, Sweeney MG, Sud R, Haworth A, Stanley E, Cea G, Davis MB, Hanna MG. What causes aramyotonia in the United Kingdom? Common and new SCN4A mutations revealed. Neurology 2008;70:50-3. Go to original source... Go to PubMed...
    14. Eaholtz G, Sheuer T, Catterall WA. Restoration of inactivation and block of open sodium channles by an inactivation gate peptide. Neuron 1994;12: 1041-8. Go to original source... Go to PubMed...
    15. Dice MS, Abbruzzese JL, Wheeler JT, Groome JR, Fujimoto E, Ruben PC. Temperature- sensitive defects in paramyotonia congenita mutants R1448C and T1313M. Muscle Nerve 2004;30:277-88. Go to original source... Go to PubMed...
    16. Hayward LJ, Brown RH, Cannon SC. Slow inactivation differs among mutant Na channles associated with myotonia and periodic paralysis. Biophys J 1997;72:1204-19. Go to original source... Go to PubMed...
    17. Hayward LJ, Brown RH, cannon SC. Inactivation deffects caused by myotonia-associated mutations in the sodium channel III-IV linker. J General Physiol 1996;107: 559-76. Go to original source... Go to PubMed...
    18. Mitrovic N, George AL Jr, Lerche H, Wagner S, Fahlke C, Lehmann-Horn F. Different effects on gating of three myotonia causing mutations in the inactivation gate of the human muscle sodium channel. J Physiol 1995; 487:107-14. Go to original source... Go to PubMed...
    19. Hayward LJ, Sandoval GM,Cannon SC. Defective slow inactivation of sodium channels contributes to familial periodic paralysis. Neurology 1999; 52:1447-53. Go to original source... Go to PubMed...

    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.


    Return to the content