Heteromeric Kv7.2 current changes caused by loss-of-function of KCNQ2 mutations are correlated with long-term neurodevelopmental outcomes

doi:10.1038/s41598-020-70212-w

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24410

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24410

Title:	Heteromeric Kv7.2 current changes caused by loss-of-function of KCNQ2 mutations are correlated with long-term neurodevelopmental outcomes
Authors:	Lee, IC;Yang, JJ;Wong, SH;Liou, YM;Li, SY
Date:	2020
Issue Date:	2022-08-09T08:01:50Z (UTC)
Publisher:	NATURE PUBLISHING GROUP
ISSN:	2045-2322
Abstract:	Pediatric epilepsy caused by KCNQ2 mutations can manifest benign familial neonatal convulsions (BFNC) to neonatal-onset epileptic encephalopathy (EE). Patients might manifest mild to profound neurodevelopmental disabilities. We analysed c.853C>A (P285T) and three mutations that cause KCNQ2 protein changes in the 247 position: c.740C>T (S247L), c.740C>A (S247X), and c.740C>G (S247W). S247L, S247W, and P285T cause neonatal-onset EE and poor neurodevelopmental outcomes; S247X cause BFNC and normal outcome. We investigated the phenotypes correlated with human embryonic kidney 293 (HEK293) cell functional current changes. More cell-current changes and a worse conductance curve were present in the homomeric transfected S247X than in S247L, S247W, and P285T. But in the heteromeric channel, S247L, S247W and P285T had more current impairments than did S247X. The protein expressions of S247X were nonfunctional. The outcomes were most severe in S247L and S247W, and severity was correlated with heteromeric current. Current changes were more significant in cells with homomeric S247X, but currents were rescued after heteromeric transfection of KCNQ2 and KCNQ3. This was not the case in cells with S247L, S247W. Our findings support that homomeric current changes are common in KCNQ2 neonatal-onset EE and KCNQ2 BFNC; however, heteromeric functional current changes are correlated with long-term neurodevelopmental outcomes.
URI:	http://dx.doi.org/10.1038/s41598-020-70212-w https://www.webofscience.com/wos/woscc/full-record/WOS:000561428300030 https://ir.csmu.edu.tw:8080/handle/310902500/24410
Relation:	SCIENTIFIC REPORTS ,2020 ,v10 ,issue 1
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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