Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head
DC Field | Value | Language |
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dc.contributor.author | Mah, Wayne | - |
dc.contributor.author | Sonkusare, Swapnil K. | - |
dc.contributor.author | Wang, Tracy | - |
dc.contributor.author | Azeddine, Bouziane | - |
dc.contributor.author | Pupavac, Mihaela | - |
dc.contributor.author | Carrot-Zhang, Jian | - |
dc.contributor.author | Hong, Kwangseok | - |
dc.contributor.author | Majewski, Jacek | - |
dc.contributor.author | Harvey, Edward J. | - |
dc.contributor.author | Russell, Laura | - |
dc.contributor.author | Chalk, Colin | - |
dc.contributor.author | Rosenblatt, David S. | - |
dc.contributor.author | Nelson, Mark T. | - |
dc.contributor.author | Seguin, Chantal | - |
dc.date.accessioned | 2021-06-18T08:43:59Z | - |
dc.date.available | 2021-06-18T08:43:59Z | - |
dc.date.issued | 2016-10 | - |
dc.identifier.issn | 0022-2593 | - |
dc.identifier.issn | 1468-6244 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/45660 | - |
dc.description.abstract | Background Osteonecrosis of the femoral head is a debilitating disease that involves impaired blood supply to the femoral head and leads to femoral head collapse. Methods We use whole-exome sequencing and Sanger sequencing to analyse a family with inherited osteonecrosis of the femoral head and fluorescent Ca2+ imaging to functionally characterise the variant protein. Results We report a family with four siblings affected with inherited osteonecrosis of the femoral head and the identification of a c.2480_2483delCCCG frameshift deletion followed by a c.2486T>A substitution in one allele of the transient receptor potential vanilloid 4 (TRPV4) gene. TRPV4 encodes a Ca2+-permeable cation channel known to play a role in vasoregulation and osteoclast differentiation. While pathogenic TRPV4 mutations affect the skeletal or nervous systems, association with osteonecrosis of the femoral head is novel. Functional measurements of Ca2+ influx through mutant TRPV4 channels in HEK293 cells and patient-derived dermal fibroblasts identified a TRPV4 gain of function. Analysis of channel open times, determined indirectly from measurement of TRPV4 activity within a cluster of TRPV4 channels, revealed that the TRPV4 gain of function was caused by longer channel openings. Conclusions These findings identify a novel TRPV4 mutation implicating TRPV4 and altered calcium homeostasis in the pathogenesis of osteonecrosis while reinforcing the importance of TRPV4 in bone diseases and vascular endothelium. | - |
dc.format.extent | 5 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | BMJ PUBLISHING GROUP | - |
dc.title | Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head | - |
dc.type | Article | - |
dc.identifier.doi | 10.1136/jmedgenet-2016-103829 | - |
dc.identifier.bibliographicCitation | JOURNAL OF MEDICAL GENETICS, v.53, no.10, pp 705 - 709 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.wosid | 000385958500009 | - |
dc.identifier.scopusid | 2-s2.0-84977599013 | - |
dc.citation.endPage | 709 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 705 | - |
dc.citation.title | JOURNAL OF MEDICAL GENETICS | - |
dc.citation.volume | 53 | - |
dc.type.docType | Article | - |
dc.publisher.location | 영국 | - |
dc.subject.keywordAuthor | TRPV4 | - |
dc.subject.keywordAuthor | osteonecrosis of the femoral head | - |
dc.subject.keywordAuthor | novel mutation | - |
dc.subject.keywordAuthor | calcium channel | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | LEUKEMIA | - |
dc.subject.keywordPlus | NECROSIS | - |
dc.subject.keywordPlus | DOMAIN | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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