{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:01:02Z","timestamp":1791907262365,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Distal arthrogryposis (DA) is comprised of a group of rare developmental disorders in muscle, characterized by multiple congenital contractures of the distal limbs. Fast skeletal muscle troponin\u2010T (TNNT3) protein is abundantly expressed in skeletal muscle and plays an important role in DA. Missense variants in <jats:italic>TNNT3<\/jats:italic> are associated with DA, but few studies have fully clarified its pathogenic role.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sanger sequencing was performed in three generation of a Chinese family with DA. To determine how the p.R63C variant contributed to DA, we identified a variant in <jats:italic>TNNT3<\/jats:italic> (NM_006757.4): c.187C&gt;T (p.R63C). And then we investigated the effects of the arginine to cysteine substitution on the distribution pattern and the half\u2010life of TNNT3 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The protein levels of TNNT3 in affected family members were 0.8\u2010fold higher than that without the disorder. TNNT3 protein could be degraded by the ubiquitin\u2010proteasome complex, and the p.R63C variant did not change TNNT3 nuclear localization, but significantly prolonged its half\u2010life from 2.5 to 7\u00a0h, to promote its accumulation in the nucleus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The p.R63C variant increased the stability of TNNT3 and promoted nuclear accumulation, which suggested its role in DA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24089","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T07:44:07Z","timestamp":1636703047000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The distal arthrogryposis\u2010linked p.R63C variant promotes the stability and nuclear accumulation of TNNT3"],"prefix":"10.1002","volume":"35","author":[{"given":"Jinfang","family":"Lu","sequence":"first","affiliation":[{"name":"Wenzhou Key Laboratory of 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