FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2887831401> ?p ?o ?g. }

• W2887831401 abstract "HCN channels are highly expressed and functionally relevant in neurons and increasing evidence demonstrates their involvement in the etiology of human epilepsies. Among HCN isoforms, HCN4 is important in cardiac tissue, where it underlies pacemaker activity. Despite being expressed also in deep structures of the brain, mutations of this channel functionally shown to be associated with epilepsy have not been reported yet. Using Next Generation Sequencing for the screening of patients with idiopathic epilepsy, we identified the p.Arg550Cys (c.1648C>T) heterozygous mutation on HCN4 in two brothers affected by benign myoclonic epilepsy of infancy. Functional characterization in heterologous expression system and in neurons showed that the mutation determines a loss of function of HCN4 contribution to activity and an increase of neuronal discharge, potentially predisposing to epilepsy. Expressed in cardiomyocytes, mutant channels activate at slightly more negative voltages than wild-type (WT), in accordance with borderline bradycardia. While HCN4 variants have been frequently associated with cardiac arrhythmias, these data represent the first experimental evidence that functional alteration of HCN4 can also be involved in human epilepsy through a loss-of-function effect and associated increased neuronal excitability. Since HCN4 appears to be highly expressed in deep brain structures only early during development, our data provide a potential explanation for a link between dysfunctional HCN4 and infantile epilepsy. These findings suggest that it may be useful to include HCN4 screening to extend the knowledge of the genetic causes of infantile epilepsies, potentially paving the way for the identification of innovative therapeutic strategies." @default.
• W2887831401 created "2018-08-22" @default.
• W2887831401 creator A5011354593 @default.
• W2887831401 creator A5013776228 @default.
• W2887831401 creator A5016315071 @default.
• W2887831401 creator A5025574771 @default.
• W2887831401 creator A5027362336 @default.
• W2887831401 creator A5033623125 @default.
• W2887831401 creator A5035870058 @default.
• W2887831401 creator A5041808669 @default.
• W2887831401 creator A5043017488 @default.
• W2887831401 creator A5048792850 @default.
• W2887831401 creator A5049237819 @default.
• W2887831401 creator A5052634729 @default.
• W2887831401 creator A5062771449 @default.
• W2887831401 creator A5070526279 @default.
• W2887831401 creator A5071048677 @default.
• W2887831401 creator A5078307231 @default.
• W2887831401 creator A5079430472 @default.
• W2887831401 creator A5080310562 @default.
• W2887831401 creator A5080421274 @default.
• W2887831401 creator A5081473300 @default.
• W2887831401 date "2018-08-06" @default.
• W2887831401 modified "2023-10-10" @default.
• W2887831401 title "A Loss-of-Function HCN4 Mutation Associated With Familial Benign Myoclonic Epilepsy in Infancy Causes Increased Neuronal Excitability" @default.
• W2887831401 cites W1492129792 @default.
• W2887831401 cites W1503574481 @default.
• W2887831401 cites W1548374789 @default.
• W2887831401 cites W1590970671 @default.
• W2887831401 cites W1966728711 @default.
• W2887831401 cites W1976672206 @default.
• W2887831401 cites W1978494722 @default.
• W2887831401 cites W1979038289 @default.
• W2887831401 cites W1979411530 @default.
• W2887831401 cites W1980226003 @default.
• W2887831401 cites W1983786684 @default.
• W2887831401 cites W1986921088 @default.
• W2887831401 cites W1989026211 @default.
• W2887831401 cites W1991176458 @default.
• W2887831401 cites W1995469233 @default.
• W2887831401 cites W1999319818 @default.
• W2887831401 cites W2002454145 @default.
• W2887831401 cites W2003082472 @default.
• W2887831401 cites W2004754041 @default.
• W2887831401 cites W2010973605 @default.
• W2887831401 cites W2014619474 @default.
• W2887831401 cites W2014880992 @default.
• W2887831401 cites W2017855292 @default.
• W2887831401 cites W2025587278 @default.
• W2887831401 cites W2030834152 @default.
• W2887831401 cites W2034105640 @default.
• W2887831401 cites W2035474677 @default.
• W2887831401 cites W2036743808 @default.
• W2887831401 cites W2051514127 @default.
• W2887831401 cites W2051841729 @default.
• W2887831401 cites W2054498084 @default.
• W2887831401 cites W2060519254 @default.
• W2887831401 cites W2070015860 @default.
• W2887831401 cites W2072477899 @default.
• W2887831401 cites W2073059074 @default.
• W2887831401 cites W2073935683 @default.
• W2887831401 cites W2085774451 @default.
• W2887831401 cites W2091651584 @default.
• W2887831401 cites W2096975778 @default.
• W2887831401 cites W2100522812 @default.
• W2887831401 cites W2111796184 @default.
• W2887831401 cites W2112196515 @default.
• W2887831401 cites W2114154551 @default.
• W2887831401 cites W2115853505 @default.
• W2887831401 cites W2123122813 @default.
• W2887831401 cites W2124585290 @default.
• W2887831401 cites W2135491838 @default.
• W2887831401 cites W2142911450 @default.
• W2887831401 cites W2144416533 @default.
• W2887831401 cites W2148622919 @default.
• W2887831401 cites W2149160476 @default.
• W2887831401 cites W2150156071 @default.
• W2887831401 cites W2157578689 @default.
• W2887831401 cites W2158022157 @default.
• W2887831401 cites W2161201932 @default.
• W2887831401 cites W2161628727 @default.
• W2887831401 cites W2165340969 @default.
• W2887831401 cites W2168473939 @default.
• W2887831401 cites W2171502806 @default.
• W2887831401 cites W2173794755 @default.
• W2887831401 cites W2316099676 @default.
• W2887831401 cites W2411795213 @default.
• W2887831401 cites W2587877487 @default.
• W2887831401 cites W2735578441 @default.
• W2887831401 cites W2742376065 @default.
• W2887831401 cites W2766563069 @default.
• W2887831401 cites W2809363379 @default.
• W2887831401 cites W4232492284 @default.
• W2887831401 cites W4239594659 @default.
• W2887831401 cites W4244689590 @default.
• W2887831401 cites W4253024663 @default.
• W2887831401 doi "https://doi.org/10.3389/fnmol.2018.00269" @default.
• W2887831401 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6089338" @default.
• W2887831401 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30127718" @default.
• W2887831401 hasPublicationYear "2018" @default.

• next