Myotonia congenita and periodic hypokalemia paralysis in a consanguineous marriage pedigree: Coexistence of a novel CLCN1 mutation and an SCN4A mutation.
- Resource Type
- Article
- Authors
- Zhao, Chenyu; Tang, DongFang; Huang, Hui; Tang, Haiyan; Yang, Yuan; Yang, Min; Luo, Yingying; Tao, Huai; Tang, Jianguang; Zhou, Xi; Shi, Xiaoliu
- Source
- PLoS ONE. 5/14/2020, Vol. 15 Issue 5, p1-13. 13p.
- Subject
- *CONSANGUINITY
*GENETIC mutation
*SODIUM channels
*EXOMES
*PARALYSIS
*CHLORIDE channels
*GENEALOGY
- Language
- ISSN
- 1932-6203
Myotonia congenita and hypokalemic periodic paralysis type 2 are both rare genetic channelopathies caused by mutations in the CLCN1 gene encoding voltage-gated chloride channel CLC-1 and the SCN4A gene encoding voltage-gated sodium channel Nav1.4. The patients with concomitant mutations in both genes manifested different unique symptoms from mutations in these genes separately. Here, we describe a patient with myotonia and periodic paralysis in a consanguineous marriage pedigree. By using whole-exome sequencing, a novel F306S variant in the CLCN1 gene and a known R222W mutation in the SCN4A gene were identified in the pedigree. Patch clamp analysis revealed that the F306S mutant reduced the opening probability of CLC-1 and chloride conductance. Our study expanded the CLCN1 mutation database. We emphasized the value of whole-exome sequencing for differential diagnosis in atypical myotonic patients. [ABSTRACT FROM AUTHOR]