A case of non-dystrophic myotonia with concomitant mutations in the SCN4A and CLCN1 genes
| Autor: | Shigehisa Mitake, Hiroyuki Yuasa, Tomomasa Ikeda, Carine Dalle, Masanori P. Takahashi, Hideki Mochizuki, Yosuke Kokunai, Yuto Uchida, Bertrand Fontaine, Tomoya Kubota, Hideki Kato, Yuta Madokoro, Sophie Nicole |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male musculoskeletal diseases 0301 basic medicine Proband congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Nav1.4 DNA Mutational Analysis Biology Myotonia 03 medical and health sciences 0302 clinical medicine Channelopathy Chloride Channels Internal medicine medicine Humans NAV1.4 Voltage-Gated Sodium Channel CLCN1 Electromyography Myotonia congenita Periodic paralysis Evoked Potentials Motor medicine.disease 030104 developmental biology Endocrinology Neurology Paramyotonia congenita Mutation Exercise Test biology.protein Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Journal of the Neurological Sciences. 369:254-258 |
| ISSN: | 0022-510X |
| DOI: | 10.1016/j.jns.2016.08.030 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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