Cited 23 times in
Whole-exome sequencing identifies two novel mutations in KCNQ4 in individuals with nonsyndromic hearing loss
DC Field | Value | Language |
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dc.contributor.author | 정진세 | - |
dc.contributor.author | 김성헌 | - |
dc.contributor.author | 최재영 | - |
dc.contributor.author | 지헌영 | - |
dc.date.accessioned | 2018-12-03T16:57:58Z | - |
dc.date.available | 2018-12-03T16:57:58Z | - |
dc.date.issued | 2018 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/165996 | - |
dc.description.abstract | Mutations in potassium voltage-gated channel subfamily Q member 4 (KCNQ4) are etiologically linked to a type of nonsyndromic hearing loss, deafness nonsyndromic autosomal dominant 2 (DFNA2). We performed whole-exome sequencing for 98 families with hearing loss and found mutations in KCNQ4 in five families. In this study, we characterized two novel mutations in KCNQ4: a missense mutation (c.796G>T; p.Asp266Tyr) and an in-frame deletion mutation (c.259_267del; p.Val87_Asn89del). p.Asp266Tyr located in the channel pore region resulted in early onset and moderate hearing loss, whereas p.Val87_Asn89del located in the N-terminal cytoplasmic region resulted in late onset and high frequency-specific hearing loss. When heterologously expressed in HEK 293 T cells, both mutant proteins did not show defects in protein trafficking to the plasma membrane or in interactions with wild-type (WT) KCNQ4 channels. Patch-clamp analysis demonstrated that both p.Asp266Tyr and p.Val87_Asn89del mutant channels lost conductance and were completely unresponsive to KCNQ activators, such as retigabine, zinc pyrithione, and ML213. Channels assembled from WT-p.Asp266Tyr concatemers, like those from WT-WT concatemers, exhibited conductance and responsiveness to KCNQ activators. However, channels assembled from WT-p.Val87_Asn89del concatemers showed impaired conductance, suggesting that p.Val87_Asn89del caused complete loss-of-function with a strong dominant-negative effect on functional WT channels. Therefore, the main pathological mechanism may be related to loss of K+ channel activity, not defects in trafficking. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Whole-exome sequencing identifies two novel mutations in KCNQ4 in individuals with nonsyndromic hearing loss | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Otorhinolaryngology (이비인후과학교실) | - |
dc.contributor.googleauthor | Jinsei Jung | - |
dc.contributor.googleauthor | Hyun Been Choi | - |
dc.contributor.googleauthor | Young Ik Koh | - |
dc.contributor.googleauthor | John Hoon Rim | - |
dc.contributor.googleauthor | Hye Ji Choi | - |
dc.contributor.googleauthor | Sung Huhn Kim | - |
dc.contributor.googleauthor | Jae Hyun Lee | - |
dc.contributor.googleauthor | Jieun An | - |
dc.contributor.googleauthor | Ami Kim | - |
dc.contributor.googleauthor | Joon Suk Lee | - |
dc.contributor.googleauthor | Sun Young Joo | - |
dc.contributor.googleauthor | Seyoung Yu | - |
dc.contributor.googleauthor | Jae Young Choi | - |
dc.contributor.googleauthor | Tong Mook Kang | - |
dc.contributor.googleauthor | Heon Yung Gee | - |
dc.identifier.doi | 10.1038/s41598-018-34876-9 | - |
dc.contributor.localId | A03742 | - |
dc.contributor.localId | A00589 | - |
dc.contributor.localId | A04173 | - |
dc.contributor.localId | A03971 | - |
dc.relation.journalcode | J02646 | - |
dc.identifier.eissn | 2045-2322 | - |
dc.identifier.pmid | 30413759 | - |
dc.contributor.alternativeName | Jung, Jinsei | - |
dc.contributor.affiliatedAuthor | 정진세 | - |
dc.contributor.affiliatedAuthor | 김성헌 | - |
dc.contributor.affiliatedAuthor | 최재영 | - |
dc.contributor.affiliatedAuthor | 지헌영 | - |
dc.citation.volume | 8 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 16659 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, Vol.8(1) : 16659, 2018 | - |
dc.identifier.rimsid | 57875 | - |
dc.type.rims | ART | - |
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