Open AccessMyotonia congenita and periodic hypokalemia paralysis in a consanguineous marriage pedigree: Coexistence of a novel CLCN1 mutation and an SCN4A mutation
Author(s) -
Chenyu Zhao,
Dongfang Tang,
Hui Huang,
Haiyan Tang,
Yuan Yang,
Min Yang,
Yingying Luo,
Huai Tao,
Jianguang Tang,
Xi Zhou,
Xiaoliu Shi
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0233017
Subject(s) - myotonia congenita , genetics , mutation , exome sequencing , exome , myotonia , biology , periodic paralysis , gene , medicine , paralysis , surgery , myotonic dystrophy
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 Na v 1.4. 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.