Wagnon, JL;
Mencacci, NE;
Barker, BS;
Wengert, ER;
Bhatia, KP;
Balint, B;
Carecchio, M;
... Meisler, MH; + view all
(2018)
Partial loss-of-function of sodium channel SCN8A in familial isolated myoclonus.
Hum Mutat
, 39
(7)
pp. 965-969.
10.1002/humu.23547.
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Abstract
Variants in the neuronal sodium channel gene SCN8A have been implicated in several neurological disorders. Early infantile epileptic encephalopathy type 13 results from de novo gain-of-function mutations that alter the biophysical properties of the channel. Complete loss-of-function variants of SCN8A have been identified in cases of isolated intellectual disability. We now report a novel heterozygous SCN8A variant, p.Pro1719Arg, in a small pedigree with five family members affected with autosomal dominant upper limb isolated myoclonus without seizures or cognitive impairment. Functional analysis of the p.Pro1719Arg variant in transfected neuron-derived cells demonstrated greatly reduced Nav 1.6 channel activity without altered gating properties. Hypomorphic alleles of Scn8a in the mouse are known to result in similar movement disorders. This study expands the phenotypic and functional spectrum of SCN8A variants to include inherited nonepileptic isolated myoclonus. SCN8A can be considered as a candidate gene for isolated movement disorders without seizures.
| Type: | Article |
|---|---|
| Title: | Partial loss-of-function of sodium channel SCN8A in familial isolated myoclonus. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/humu.23547 |
| Publisher version: | https://doi.org/10.1002/humu.23547 |
| Language: | English |
| Additional information: | © 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| Keywords: | Nav1.6, movement disorder, myoclonus, sodium channel |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10050816 |
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