Publications
Detailed Information
Characteristics of novel KCNQ4 variants showing a distinct hearing loss phenotype : 새로운 KCNQ4 돌연 변이의 발견 및 난청 유형 분석
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 오승하 | - |
dc.contributor.author | 박미나 | - |
dc.date.accessioned | 2017-10-27T17:04:41Z | - |
dc.date.available | 2017-10-27T17:04:41Z | - |
dc.date.issued | 2017-08 | - |
dc.identifier.other | 000000146066 | - |
dc.identifier.uri | https://hdl.handle.net/10371/137061 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 의과대학 의학과, 2017. 8. 오승하. | - |
dc.description.abstract | KCNQ4 mutations lead to autosomal dominant non-syndromic, and typically progressive and high-frequency, hearing loss (HL). In this report, I identified two novel KCNQ4 mutations, namely p.R331Q and p.811_816del, in two different families. One mutation in the C-terminal region was associated with low- to mid-frequency HL and the other mutation, located in the P-loop, was associated with high frequency HL. Although I did not observe a difference in the subcellular localization of the KCNQ4 mutants p.R331Q and c.811_816del, c.811_816del protein expression was significantly decreased compared with that of wild-type KCNQ4 (KCNQ4WT) and the p.R331Q mutant. The potassium currents were significantly decreased in both the p.R331Q and c.811_816del mutants compared with KCNQ4WT, indicative of the pathogenic potential of the two variants. Based on electrophysiological data, p.R331Q and c.811_816del KCNQ4 channels showed loss of function and a dominant-negative effect when combined with functional KCNQ4WT channels. The heteromeric mutant channels assembled with WT were activated by a KCNQ4 activator (retigabine), and the degree of rescue by retigabine was stronger in the p.R331Q heteromer than in the c.811_816del heteromer. This study reports a C-terminal tail variant among KCNQ4 mutants for the first time, and broadens the audiologic phenotypic spectrum from high frequency sensorineural HL to include low- to mid-frequency sensorineural HL. | - |
dc.description.tableofcontents | Introduction 1
Materials and Methods 2 Results 9 Discussion 16 References 20 Figures 24 Abstract (Korean) 33 | - |
dc.format | application/pdf | - |
dc.format.extent | 2546748 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | Hearing loss | - |
dc.subject | KCNQ4 | - |
dc.subject | K+channel | - |
dc.subject | Mutation | - |
dc.subject | Dominant negative effect | - |
dc.subject | Rescue | - |
dc.subject.ddc | 610 | - |
dc.title | Characteristics of novel KCNQ4 variants showing a distinct hearing loss phenotype | - |
dc.title.alternative | 새로운 KCNQ4 돌연 변이의 발견 및 난청 유형 분석 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Mina Park | - |
dc.description.degree | Doctor | - |
dc.contributor.affiliation | 의과대학 의학과 | - |
dc.date.awarded | 2017-08 | - |
- Appears in Collections:
- Files in This Item:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.