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Article: Mutations in COMP cause familial carpal tunnel syndrome

TitleMutations in COMP cause familial carpal tunnel syndrome
Authors
Issue Date2020
PublisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2020, v. 11 n. 1, p. article no. 3642 How to Cite?
AbstractCarpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome, affecting a large proportion of the general population. Genetic susceptibility has been implicated in CTS, but the causative genes remain elusive. Here, we report the identification of two mutations in cartilage oligomeric matrix protein (COMP) that segregate with CTS in two large families with or without multiple epiphyseal dysplasia (MED). Both mutations impair the secretion of COMP by tenocytes, but the mutation associated with MED also perturbs its secretion in chondrocytes. Further functional characterization of the CTS-specific mutation reveals similar histological and molecular changes of tendons/ligaments in patients' biopsies and the mouse models. The mutant COMP fails to oligomerize properly and is trapped in the ER, resulting in ER stress-induced unfolded protein response and cell death, leading to inflammation, progressive fibrosis and cell composition change in tendons/ligaments. The extracellular matrix (ECM) organization is also altered. Our studies uncover a previously unrecognized mechanism in CTS pathogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/304896
ISSN
2020 Impact Factor: 14.919
2020 SCImago Journal Rankings: 5.559
PubMed Central ID
Errata

 

DC FieldValueLanguage
dc.contributor.authorLi, C-
dc.contributor.authorWang, N-
dc.contributor.authorSchaffer, AA-
dc.contributor.authorLiu, X-
dc.contributor.authorZhao, Z-
dc.contributor.authorElliott, G-
dc.contributor.authorGarrett, L-
dc.contributor.authorChoi, NT-
dc.contributor.authorWang, Y-
dc.contributor.authorWang, Y-
dc.contributor.authorWang, C-
dc.contributor.authorWang, J-
dc.contributor.authorChan, D-
dc.contributor.authorSu, P-
dc.contributor.authorCui, S-
dc.contributor.authorYang, Y-
dc.contributor.authorGao, B-
dc.date.accessioned2021-10-05T02:36:46Z-
dc.date.available2021-10-05T02:36:46Z-
dc.date.issued2020-
dc.identifier.citationNature Communications, 2020, v. 11 n. 1, p. article no. 3642-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/304896-
dc.description.abstractCarpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome, affecting a large proportion of the general population. Genetic susceptibility has been implicated in CTS, but the causative genes remain elusive. Here, we report the identification of two mutations in cartilage oligomeric matrix protein (COMP) that segregate with CTS in two large families with or without multiple epiphyseal dysplasia (MED). Both mutations impair the secretion of COMP by tenocytes, but the mutation associated with MED also perturbs its secretion in chondrocytes. Further functional characterization of the CTS-specific mutation reveals similar histological and molecular changes of tendons/ligaments in patients' biopsies and the mouse models. The mutant COMP fails to oligomerize properly and is trapped in the ER, resulting in ER stress-induced unfolded protein response and cell death, leading to inflammation, progressive fibrosis and cell composition change in tendons/ligaments. The extracellular matrix (ECM) organization is also altered. Our studies uncover a previously unrecognized mechanism in CTS pathogenesis.-
dc.languageeng-
dc.publisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsNature Communications. Copyright © Nature Research: Fully open access journals.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleMutations in COMP cause familial carpal tunnel syndrome-
dc.typeArticle-
dc.identifier.emailChoi, NT: vntchoi@hku.hk-
dc.identifier.emailChan, D: chand@hku.hk-
dc.identifier.emailGao, B: gaobo@hku.hk-
dc.identifier.authorityChan, D=rp00540-
dc.identifier.authorityGao, B=rp02012-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-020-17378-z-
dc.identifier.pmid32686688-
dc.identifier.pmcidPMC7371736-
dc.identifier.scopuseid_2-s2.0-85088245609-
dc.identifier.hkuros325773-
dc.identifier.volume11-
dc.identifier.issue1-
dc.identifier.spagearticle no. 3642-
dc.identifier.epagearticle no. 3642-
dc.publisher.placeUnited Kingdom-
dc.relation.erratumdoi:10.1038/s41467-020-17845-7-

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