A case of non-dystrophic myotonia with concomitant mutations in the SCN4A and CLCN1 genes.

Abstract

Non-dystrophic myotonias are caused by mutations of either the skeletal muscle chloride (CLCN1) or sodium channel (SCN4A) gene. They exhibit several distinct phenotypes, including myotonia congenita, paramyotonia congenita and sodium channel myotonia, and a genotype-phenotype correlation has been established. However, there are atypical cases that do not fit with the standard classification. We report a case of 27-year-old male who had non-dystrophic myotonia with periodic paralysis and two heterozygous mutations, E950K in CLCN1 and F1290L in SCN4A. His mother, who exhibited myotonia without paralytic attack, only harbored E950K, and no mutations were identified in his asymptomatic father. Therefore, the E950K mutation was presumed to be pathogenic, although it was reported as an extremely rare genetic variant. The proband experienced paralytic attacks that lasted for weeks and were less likely to be caused by CLCN1 mutation alone. Functional analysis of the F1290L mutant channel heterologously expressed in cultured cells revealed enhanced activation inducing membrane hyperexcitability. We therefore propose that the two mutations had additive effects on membrane excitability that resulted in more prominent myotonia in the proband. Our case stresses the value of performing genetic analysis of both CLCN1 and SCN4A genes for myotonic patients with an atypical phenotype.

• Authors: Hideki Kato, Yosuke Kokunai, Carine Dalle, Tomoya Kubota, Yuta Madokoro, Hiroyuki Yuasa, Yuto Uchida, Tomomasa Ikeda, Hideki Mochizuki, Sophie Nicole, Bertrand Fontaine, Masanori P Takahashi, Shigehisa Mitake
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 369 Pg. 254-258 (Oct 15 2016) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 27653901 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• CLC-1 channel
• Chloride Channels
• NAV1.4 Voltage-Gated Sodium Channel
• SCN4A protein, human

Topics

• Adult
• Chloride Channels (genetics)
• DNA Mutational Analysis
• Electromyography
• Evoked Potentials, Motor (genetics)
• Exercise Test
• Humans
• Male
• Mutation (genetics)
• Myotonia (genetics, physiopathology)
• NAV1.4 Voltage-Gated Sodium Channel (genetics)