Skip to main content
NCBI home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2001 May;70(5):618–623. doi: 10.1136/jnnp.70.5.618

Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica

J Kim 1, Y Hahn 1, E Sohn 1, Y Lee 1, J Yun 1, J Kim 1, J Chung 1
PMCID: PMC1737343  PMID: 11309455

Abstract

OBJECTIVES—Patients with paralysis periodica paramyotonica exhibit a clinical syndrome with characteristics of both hyperkalaemic periodic paralysis and paramyotonia congenita. In several types of periodic paralysis associated with hyperkalaemia, mutations in the skeletal muscle sodium channel (SCN4A) gene have been previously reported. Phenotypic variations of mutations in SCN4A, however, have not been described yet. The present study aimed to evaluate genetic variations in a family with clinical and electrophysiological characteristics of paralysis periodica paramyotonia.
METHODS—Seven members of a family affected with symptoms of paralysis periodica paramyotonia were studied by electrophysiological and genetic analyses. There were increased serum potassium concentrations in four members during paralytic attacks induced by hyperkalaemic periodic paralysis provocation tests. Short exercise tests before and after cold immersion were carried out in four patients to distinguish electrophysiological characteristics of hyperkalaemic periodic paralysis and paramyotonia. Sequencing analyses of SCN4A were performed on one patient and a normal control to identify polymorphisms. Restriction fragment length polymorphism (RFLP) analysis was then performed at the identified polymorphic sites.
RESULTS—Electrophysiological studies showed both exercise sensitivity and temperature sensitivity. Compound motor action potential (CMAP) amplitudes were decreased (7.3%-28.6%) after short exercise tests. The CMAP amplitudes were even more severely decreased (21.7%-56.5%) in short exercise tests after cold exposure. Three polymorphic sites, Gln371Glu, Thr704Met, and Aspl376Asn were identified in SCN4A. RFLP analyses showed that all affected patients carried the Thr704Met mutation, whereas unaffected family members and a normal control did not.
CONCLUSION— Phenotypic variation of the Thr704Met mutation, which was previously reported in patients with hyperkalaemic periodic paralysis, is described in a family affected with paralysis periodica paramyotonia.



Full Text

The Full Text of this article is available as a PDF (169.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cannon S. C. Ion-channel defects and aberrant excitability in myotonia and periodic paralysis. Trends Neurosci. 1996 Jan;19(1):3–10. doi: 10.1016/0166-2236(96)81859-5. [DOI] [PubMed] [Google Scholar]
  2. Ebers G. C., George A. L., Barchi R. L., Ting-Passador S. S., Kallen R. G., Lathrop G. M., Beckmann J. S., Hahn A. F., Brown W. F., Campbell R. D. Paramyotonia congenita and hyperkalemic periodic paralysis are linked to the adult muscle sodium channel gene. Ann Neurol. 1991 Dec;30(6):810–816. doi: 10.1002/ana.410300610. [DOI] [PubMed] [Google Scholar]
  3. Feero W. G., Wang J., Barany F., Zhou J., Todorovic S. M., Conwit R., Galloway G., Hausmanowa-Petrusewicz I., Fidzianska A., Arahata K. Hyperkalemic periodic paralysis: rapid molecular diagnosis and relationship of genotype to phenotype in 12 families. Neurology. 1993 Apr;43(4):668–673. doi: 10.1212/wnl.43.4.668. [DOI] [PubMed] [Google Scholar]
  4. Fontaine B., Khurana T. S., Hoffman E. P., Bruns G. A., Haines J. L., Trofatter J. A., Hanson M. P., Rich J., McFarlane H., Yasek D. M. Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene. Science. 1990 Nov 16;250(4983):1000–1002. doi: 10.1126/science.2173143. [DOI] [PubMed] [Google Scholar]
  5. George A. L., Jr, Iyer G. S., Kleinfield R., Kallen R. G., Barchi R. L. Genomic organization of the human skeletal muscle sodium channel gene. Genomics. 1993 Mar;15(3):598–606. doi: 10.1006/geno.1993.1113. [DOI] [PubMed] [Google Scholar]
  6. George A. L., Jr, Komisarof J., Kallen R. G., Barchi R. L. Primary structure of the adult human skeletal muscle voltage-dependent sodium channel. Ann Neurol. 1992 Feb;31(2):131–137. doi: 10.1002/ana.410310203. [DOI] [PubMed] [Google Scholar]
  7. George A. L., Jr, Ledbetter D. H., Kallen R. G., Barchi R. L. Assignment of a human skeletal muscle sodium channel alpha-subunit gene (SCN4A) to 17q23.1-25.3. Genomics. 1991 Mar;9(3):555–556. doi: 10.1016/0888-7543(91)90425-e. [DOI] [PubMed] [Google Scholar]
  8. Griggs R. C., Ptácek L. J. Mutations of sodium channels in periodic paralysis: can they explain the disease and predict treatment? Neurology. 1999 Apr 22;52(7):1309–1310. doi: 10.1212/wnl.52.7.1309. [DOI] [PubMed] [Google Scholar]
  9. Hudson A. J., Ebers G. C., Bulman D. E. The skeletal muscle sodium and chloride channel diseases. Brain. 1995 Apr;118(Pt 2):547–563. doi: 10.1093/brain/118.2.547. [DOI] [PubMed] [Google Scholar]
  10. Jackson C. E., Barohn R. J., Ptacek L. J. Paramyotonia congenita: abnormal short exercise test, and improvement after mexiletine therapy. Muscle Nerve. 1994 Jul;17(7):763–768. doi: 10.1002/mus.880170710. [DOI] [PubMed] [Google Scholar]
  11. Lerche H., Heine R., Pika U., George A. L., Jr, Mitrovic N., Browatzki M., Weiss T., Rivet-Bastide M., Franke C., Lomonaco M. Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker. J Physiol. 1993 Oct;470:13–22. doi: 10.1113/jphysiol.1993.sp019843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McClatchey A. I., McKenna-Yasek D., Cros D., Worthen H. G., Kuncl R. W., DeSilva S. M., Cornblath D. R., Gusella J. F., Brown R. H., Jr Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel. Nat Genet. 1992 Oct;2(2):148–152. doi: 10.1038/ng1092-148. [DOI] [PubMed] [Google Scholar]
  13. Ricker K., Moxley R. T., 3rd, Heine R., Lehmann-Horn F. Myotonia fluctuans. A third type of muscle sodium channel disease. Arch Neurol. 1994 Nov;51(11):1095–1102. doi: 10.1001/archneur.1994.00540230033009. [DOI] [PubMed] [Google Scholar]
  14. Ricker K., Rohkamm R., Böhlen R. Adynamia episodica and paralysis periodica paramyotonica. Neurology. 1986 May;36(5):682–686. doi: 10.1212/wnl.36.5.682. [DOI] [PubMed] [Google Scholar]
  15. Sampaolo S., Puca A. A., Nigro V., Cappa V., Sannino V., Sanges G., Bonavita V., Di Iorio G. Lack of sodium channel mutation in an Italian family with paramyotonia congenita. Neurology. 1999 Oct 22;53(7):1549–1555. doi: 10.1212/wnl.53.7.1549. [DOI] [PubMed] [Google Scholar]
  16. de Silva S. M., Kuncl R. W., Griffin J. W., Cornblath D. R., Chavoustie S. Paramyotonia congenita or hyperkalemic periodic paralysis? Clinical and electrophysiological features of each entity in one family. Muscle Nerve. 1990 Jan;13(1):21–26. doi: 10.1002/mus.880130106. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES