Cited 21 times in
Novel COCH p.V123E Mutation, Causative of DFNA9 Sensorineural Hearing Loss and Vestibular Disorder, Shows Impaired Cochlin Post-Translational Cleavage and Secretion
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김한상 | - |
dc.contributor.author | 이민구 | - |
dc.contributor.author | 정진세 | - |
dc.contributor.author | 최재영 | - |
dc.date.accessioned | 2018-03-26T16:48:06Z | - |
dc.date.available | 2018-03-26T16:48:06Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 1059-7794 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/156828 | - |
dc.description.abstract | DFNA9 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.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Wiley-Liss | - |
dc.relation.isPartOf | HUMAN MUTATION | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Amino Acid Sequence | - |
dc.subject.MESH | Amino Acid Substitution* | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Codon* | - |
dc.subject.MESH | Extracellular Matrix Proteins/chemistry | - |
dc.subject.MESH | Extracellular Matrix Proteins/genetics* | - |
dc.subject.MESH | Extracellular Matrix Proteins/metabolism | - |
dc.subject.MESH | Genes, Dominant | - |
dc.subject.MESH | Hearing Loss, Sensorineural/diagnosis | - |
dc.subject.MESH | Hearing Loss, Sensorineural/genetics* | - |
dc.subject.MESH | Hearing Loss, Sensorineural/metabolism | - |
dc.subject.MESH | Hearing Tests | - |
dc.subject.MESH | High-Throughput Nucleotide Sequencing | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Magnetic Resonance Imaging | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Mutation* | - |
dc.subject.MESH | Pedigree | - |
dc.subject.MESH | Protein Multimerization | - |
dc.subject.MESH | Protein Processing, Post-Translational | - |
dc.subject.MESH | Protein Transport | - |
dc.subject.MESH | Proteolysis | - |
dc.subject.MESH | Tomography, X-Ray Computed | - |
dc.subject.MESH | Vestibular Diseases/diagnosis | - |
dc.subject.MESH | Vestibular Diseases/genetics* | - |
dc.subject.MESH | Vestibular Diseases/metabolism | - |
dc.title | Novel COCH p.V123E Mutation, Causative of DFNA9 Sensorineural Hearing Loss and Vestibular Disorder, Shows Impaired Cochlin Post-Translational Cleavage and Secretion | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Pharmacology | - |
dc.contributor.googleauthor | Jinsei Jung | - |
dc.contributor.googleauthor | Han Sang Kim | - |
dc.contributor.googleauthor | Min Goo Lee | - |
dc.contributor.googleauthor | Eun Jin Yang | - |
dc.contributor.googleauthor | Jae Young Choi | - |
dc.identifier.doi | 10.1002/humu.22855 | - |
dc.contributor.localId | A01098 | - |
dc.contributor.localId | A02781 | - |
dc.contributor.localId | A03742 | - |
dc.contributor.localId | A04173 | - |
dc.relation.journalcode | J01010 | - |
dc.identifier.eissn | 1098-1004 | - |
dc.identifier.pmid | 26256111 | - |
dc.identifier.url | http://onlinelibrary.wiley.com/doi/10.1002/humu.22855/abstract | - |
dc.subject.keyword | DFNA9 | - |
dc.subject.keyword | hearing loss | - |
dc.subject.keyword | cochlin | - |
dc.subject.keyword | post-translational cleavage | - |
dc.subject.keyword | aggrecanase | - |
dc.contributor.alternativeName | Kim, Han Sang | - |
dc.contributor.alternativeName | Lee, Min Goo | - |
dc.contributor.alternativeName | Jung, Jinsei | - |
dc.contributor.alternativeName | Choi, Jae Young | - |
dc.contributor.affiliatedAuthor | Kim, Han Sang | - |
dc.contributor.affiliatedAuthor | Lee, Min Goo | - |
dc.contributor.affiliatedAuthor | Jung, Jinsei | - |
dc.contributor.affiliatedAuthor | Choi, Jae Young | - |
dc.citation.volume | 36 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 1168 | - |
dc.citation.endPage | 1175 | - |
dc.identifier.bibliographicCitation | HUMAN MUTATION, Vol.36(12) : 1168-1175, 2015 | - |
dc.identifier.rimsid | 39956 | - |
dc.type.rims | ART | - |
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