KCNC1-related disorders: new de novo variants expand the phenotypic spectrum.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
07
05
2019
accepted:
11
05
2019
entrez:
30
7
2019
pubmed:
30
7
2019
medline:
14
5
2020
Statut:
ppublish
Résumé
A recurrent de novo missense variant in KCNC1, encoding a voltage-gated potassium channel expressed in inhibitory neurons, causes progressive myoclonus epilepsy and ataxia, and a nonsense variant is associated with intellectual disability. We identified three new de novo missense variants in KCNC1 in five unrelated individuals causing different phenotypes featuring either isolated nonprogressive myoclonus (p.Cys208Tyr), intellectual disability (p.Thr399Met), or epilepsy with myoclonic, absence and generalized tonic-clonic seizures, ataxia, and developmental delay (p.Ala421Val, three patients). Functional analyses demonstrated no measurable currents for all identified variants and dominant-negative effects for p.Thr399Met and p.Ala421Val predicting neuronal disinhibition as the underlying disease mechanism.
Identifiants
pubmed: 31353862
doi: 10.1002/acn3.50799
pmc: PMC6649617
doi:
Substances chimiques
Codon, Nonsense
0
KCNC1 protein, human
0
Shaw Potassium Channels
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1319-1326Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : FOR-2715
Pays : International
Organisme : University of Tuebingen
Pays : International
Organisme : Bundesministerium für Bildung und Forschung
ID : FKZ 01GM1907A
Pays : International
Organisme : Bundesministerium für Bildung und Forschung
ID : FKZ 01ZX1405C
Pays : International
Organisme : intramural fortüne program
ID : #
Pays : International
Organisme : intramural fortüne program
ID : 2435-0-0
Pays : International
Informations de copyright
© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
Références
Neurology. 2014 Feb 4;82(5):405-11
pubmed: 24384641
Trends Neurosci. 2001 Sep;24(9):517-26
pubmed: 11506885
Genet Med. 2016 Sep;18(9):898-905
pubmed: 26795593
Hum Genet. 2018 May;137(5):401-411
pubmed: 29796876
Ann Clin Transl Neurol. 2019 Jul;6(7):1319-1326
pubmed: 31353862
Eur J Pharmacol. 2018 Aug 15;833:255-262
pubmed: 29894724
Nat Neurosci. 2005 Oct;8(10):1335-42
pubmed: 16136041
Brain Dev. 2018 May;40(5):429-432
pubmed: 29428275
Nucleic Acids Res. 2018 Jan 4;46(D1):D1062-D1067
pubmed: 29165669
PLoS One. 2015 Mar 10;10(3):e0116599
pubmed: 25756792
Neuron. 1996 Jun;16(6):1169-77
pubmed: 8663993
Res Dev Disabil. 2011 Mar-Apr;32(2):419-36
pubmed: 21236634
PLoS One. 2011 Mar 29;6(3):e17811
pubmed: 21479265
Nat Genet. 2018 Jul;50(7):1048-1053
pubmed: 29942082
Eur J Hum Genet. 2017 May;25(5):560-564
pubmed: 28145425
Ment Retard Dev Disabil Res Rev. 2002;8(3):117-34
pubmed: 12216056
PLoS One. 2017 Nov 30;12(11):e0188978
pubmed: 29190809
Brain. 2013 Jun;136(Pt 6):1708-17
pubmed: 23687123
Nat Genet. 2015 Jan;47(1):39-46
pubmed: 25401298
Epilepsia. 2000 Jul;41(7):802-10
pubmed: 10897150
Lancet. 2012 Nov 10;380(9854):1674-82
pubmed: 23020937
Ann Neurol. 2017 May;81(5):677-689
pubmed: 28380698