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Novel COCH p.V123E Mutation, Causative of DFNA9 Sensorineural Hearing Loss and Vestibular Disorder, Shows Impaired Cochlin Post-Translational Cleavage and Secretion

DC FieldValueLanguage
dc.contributor.author김한상-
dc.contributor.author이민구-
dc.contributor.author정진세-
dc.contributor.author최재영-
dc.date.accessioned2018-03-26T16:48:06Z-
dc.date.available2018-03-26T16:48:06Z-
dc.date.issued2015-
dc.identifier.issn1059-7794-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/156828-
dc.description.abstractDFNA9 is an autosomal dominant disorder characterized by late-onset, non-syndromic hearing loss, and vestibular dysfunction. Mutations in the COCH (coagulation factor C homology) gene encoding cochlin are etiologically linked to DFNA9. Previous studies have shown that cochlin is cleaved by aggrecanase-1 during inflammation in the spleen and that the cleaved LCCL domain functions as an innate immune mediator. However, the physiological role of cochlin in the inner ear is not completely understood. Here, we report that cochlins containing DFNA9-linked mutations (p.P51S, p.V66G, p.G88E, p.I109T, p.W117R, p.V123E, and p.C162Y) demonstrate reduced cleavage by aggrecanase. Notably, in families affected with DFNA9, we found a novel COCH mutation causing p.V123E substitution in cochlin, which significantly reduced protein susceptibility to cleavage by aggrecanase (to about 20.5% of the wild-type). These results suggest that the impaired post-translational cleavage of cochlin mutants may be associated with pathological mechanisms underlying DFNA9-related sensorineural hearing loss.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherWiley-Liss-
dc.relation.isPartOfHUMAN MUTATION-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdult-
dc.subject.MESHAmino Acid Sequence-
dc.subject.MESHAmino Acid Substitution*-
dc.subject.MESHCell Line-
dc.subject.MESHCodon*-
dc.subject.MESHExtracellular Matrix Proteins/chemistry-
dc.subject.MESHExtracellular Matrix Proteins/genetics*-
dc.subject.MESHExtracellular Matrix Proteins/metabolism-
dc.subject.MESHGenes, Dominant-
dc.subject.MESHHearing Loss, Sensorineural/diagnosis-
dc.subject.MESHHearing Loss, Sensorineural/genetics*-
dc.subject.MESHHearing Loss, Sensorineural/metabolism-
dc.subject.MESHHearing Tests-
dc.subject.MESHHigh-Throughput Nucleotide Sequencing-
dc.subject.MESHHumans-
dc.subject.MESHMagnetic Resonance Imaging-
dc.subject.MESHMiddle Aged-
dc.subject.MESHMutation*-
dc.subject.MESHPedigree-
dc.subject.MESHProtein Multimerization-
dc.subject.MESHProtein Processing, Post-Translational-
dc.subject.MESHProtein Transport-
dc.subject.MESHProteolysis-
dc.subject.MESHTomography, X-Ray Computed-
dc.subject.MESHVestibular Diseases/diagnosis-
dc.subject.MESHVestibular Diseases/genetics*-
dc.subject.MESHVestibular Diseases/metabolism-
dc.titleNovel COCH p.V123E Mutation, Causative of DFNA9 Sensorineural Hearing Loss and Vestibular Disorder, Shows Impaired Cochlin Post-Translational Cleavage and Secretion-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Pharmacology-
dc.contributor.googleauthorJinsei Jung-
dc.contributor.googleauthorHan Sang Kim-
dc.contributor.googleauthorMin Goo Lee-
dc.contributor.googleauthorEun Jin Yang-
dc.contributor.googleauthorJae Young Choi-
dc.identifier.doi10.1002/humu.22855-
dc.contributor.localIdA01098-
dc.contributor.localIdA02781-
dc.contributor.localIdA03742-
dc.contributor.localIdA04173-
dc.relation.journalcodeJ01010-
dc.identifier.eissn1098-1004-
dc.identifier.pmid26256111-
dc.identifier.urlhttp://onlinelibrary.wiley.com/doi/10.1002/humu.22855/abstract-
dc.subject.keywordDFNA9-
dc.subject.keywordhearing loss-
dc.subject.keywordcochlin-
dc.subject.keywordpost-translational cleavage-
dc.subject.keywordaggrecanase-
dc.contributor.alternativeNameKim, Han Sang-
dc.contributor.alternativeNameLee, Min Goo-
dc.contributor.alternativeNameJung, Jinsei-
dc.contributor.alternativeNameChoi, Jae Young-
dc.contributor.affiliatedAuthorKim, Han Sang-
dc.contributor.affiliatedAuthorLee, Min Goo-
dc.contributor.affiliatedAuthorJung, Jinsei-
dc.contributor.affiliatedAuthorChoi, Jae Young-
dc.citation.volume36-
dc.citation.number12-
dc.citation.startPage1168-
dc.citation.endPage1175-
dc.identifier.bibliographicCitationHUMAN MUTATION, Vol.36(12) : 1168-1175, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers

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