| Autor: |
Kevin Jehasse, Kathleen Jacquerie, Alice de Froidmont, Camille Lemoine, Thierry Grisar, Katrien Stouffs, Bernard Lakaye, Vincent Seutin |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Molecular Genetics & Genomic Medicine, Vol 9, Iss 2, Pp n/a-n/a (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2324-9269 |
| DOI: |
10.1002/mgg3.1588 |
| Popis: |
ABSTRACT Background Myotonia congenita (MC) is a common channelopathy affecting skeletal muscle and which is due to pathogenic variants within the CLCN1 gene. Various alterations in the function of the channel have been reported and we here illustrate a novel one. Methods A patient presenting the symptoms of myotonia congenita was shown to bear a new heterozygous missense variant in exon 9 of the CLCN1 gene (c.1010 T > G, p.(Phe337Cys)). Confocal imaging and patch clamp recordings of transiently transfected HEK293 cells were used to functionally analyze the effect of this variant on channel properties. Results Confocal imaging showed that the F337C mutant incorporated as well as the WT channel into the plasma membrane. However, in patch clamp, we observed a smaller conductance for F337C at −80 mV. We also found a marked reduction of the fast gating component in the mutant channels, as well as an overall reduced voltage dependence. Conclusion To our knowledge, this is the first report of a mixed alteration in the biophysical properties of hClC‐1 consisting of a reduced conductance at resting potential and an almost abolished voltage dependence. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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