Publication
Title
De novo mutations in HCN1 cause early infantile epileptic encephalopathy
Author
Institution/Organisation
EuroEPINOMICS RES Consortium
Abstract
Hyperpolarization-activated, cyclic nucleotide gated (HCN) channels contribute to cationic current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of I-h, currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable earlyonset epileptic encephalopathy in humans.
Language
English
Source (journal)
Nature genetics. - New York, N.Y.
Publication
New York, N.Y. : 2014
ISSN
1061-4036
Volume/pages
46:6(2014), p. 640-645
ISI
000336870700024
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 28.08.2014
Last edited 05.09.2017
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