{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:58:11Z","timestamp":1790827091774,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ5219"],"award-info":[{"award-number":["2024JJ5219"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ40343"],"award-info":[{"award-number":["2023JJ40343"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31501017"],"award-info":[{"award-number":["31501017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["gimjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Genetics in Medicine"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.gim.2025.101537","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T23:54:51Z","timestamp":1753142091000},"page":"101537","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synostosis of joints caused by mutant FBN2 is linked to the abnormalities and misdifferentiation of articular surface cells"],"prefix":"10.1016","volume":"27","author":[{"given":"Mei","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2511-961X","authenticated-orcid":false,"given":"Yu","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8673-1589","authenticated-orcid":false,"given":"Yongjia","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"7","key":"10.1016\/j.gim.2025.101537_bib1","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1002\/humu.24383","article-title":"The fibrillinopathies: new insights with focus on the paradigm of opposing phenotypes for both FBN1 and FBN2","volume":"43","author":"Peeters","year":"2022","journal-title":"Hum Mutat"},{"issue":"6","key":"10.1016\/j.gim.2025.101537_bib2","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1083\/jcb.201003089","article-title":"Fibrillin-1 and \u22122 differentially modulate endogenous TGF-\u03b2 and BMP bioavailability during bone formation","volume":"190","author":"Nistala","year":"2010","journal-title":"J Cell Biol"},{"issue":"8","key":"10.1016\/j.gim.2025.101537_bib3","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.matbio.2008.09.579","article-title":"Bone and soft connective tissue alterations result from loss of fibrillin-2 expression","volume":"27","author":"Boregowda","year":"2008","journal-title":"Matrix Biol"},{"issue":"11","key":"10.1016\/j.gim.2025.101537_bib4","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1136\/jmedgenet-2020-107085","article-title":"Delineation of a new fibrillin-2-opathy with evidence for a role of FBN2 in the pathogenesis of carpal tunnel syndrome","volume":"58","author":"Peeters","year":"2021","journal-title":"J Med Genet"},{"issue":"7","key":"10.1016\/j.gim.2025.101537_bib5","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1136\/jmg-2024-110533","article-title":"Short stature, brachydactyly and joint contractures associated with novel FBN2 variants in two families","volume":"62","author":"Loid","year":"2025","journal-title":"J Med Genet"},{"issue":"1","key":"10.1016\/j.gim.2025.101537_bib6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41436-019-0609-8","article-title":"A clinical scoring system for congenital contractural arachnodactyly","volume":"22","author":"Meerschaut","year":"2020","journal-title":"Genet Med"},{"issue":"6","key":"10.1016\/j.gim.2025.101537_bib7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005340","article-title":"Abnormal activation of BMP signaling causes myopathy in Fbn2 null mice","volume":"11","author":"Sengle","year":"2015","journal-title":"PLoS Genet"},{"issue":"6","key":"10.1016\/j.gim.2025.101537_bib8","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00223-014-9917-9","article-title":"Osteoarthritis pathogenesis: a review of molecular mechanisms","volume":"95","author":"Xia","year":"2014","journal-title":"Calcif Tissue Int"},{"issue":"2","key":"10.1016\/j.gim.2025.101537_bib9","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.joca.2021.11.009","article-title":"Osteoarthritis year in review 2021: biology","volume":"30","author":"Jiang","year":"2021","journal-title":"Osteoarthr Cartil"},{"issue":"18","key":"10.1016\/j.gim.2025.101537_bib10","doi-asserted-by":"crossref","first-page":"4784","DOI":"10.1016\/j.cell.2021.07.038","article-title":"Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations","volume":"184","author":"Boer","year":"2021","journal-title":"Cell"},{"issue":"2","key":"10.1016\/j.gim.2025.101537_bib11","doi-asserted-by":"crossref","DOI":"10.1093\/genetics\/iyad150","article-title":"Leveraging osteoclast genetic regulatory data to identify genes with a role in osteoarthritis","volume":"225","author":"Mullin","year":"2023","journal-title":"Genetics"},{"issue":"4","key":"10.1016\/j.gim.2025.101537_bib12","doi-asserted-by":"crossref","first-page":"530","DOI":"10.2460\/ajvr.72.4.530","article-title":"Evaluation of a fibrillin 2 gene haplotype associated with hip dysplasia and incipient osteoarthritis in dogs","volume":"72","author":"Friedenberg","year":"2011","journal-title":"Am J Vet Res"},{"issue":"11","key":"10.1016\/j.gim.2025.101537_bib13","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1038\/s41436-019-0552-8","article-title":"SMAD6 is frequently mutated in nonsyndromic radioulnar synostosis","volume":"21","author":"Yang","year":"2019","journal-title":"Genet Med"},{"issue":"4","key":"10.1016\/j.gim.2025.101537_bib14","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1086\/503204","article-title":"GDF5 is a second locus for multiple-synostosis syndrome","volume":"78","author":"Dawson","year":"2006","journal-title":"Am J Hum Genet"},{"issue":"9","key":"10.1016\/j.gim.2025.101537_bib15","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1172\/JCI25118","article-title":"Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2","volume":"115","author":"Seemann","year":"2005","journal-title":"J Clin Invest"},{"issue":"4","key":"10.1016\/j.gim.2025.101537_bib16","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/jbmr.2761","article-title":"A new subtype of multiple synostoses syndrome is caused by a mutation in GDF6 that decreases its sensitivity to noggin and enhances its potency as a BMP signal","volume":"31","author":"Wang","year":"2016","journal-title":"J Bone Miner Res"},{"issue":"1","key":"10.1016\/j.gim.2025.101537_bib17","doi-asserted-by":"crossref","DOI":"10.1002\/mgg3.1850","article-title":"A genotype and phenotype analysis of SMAD6 mutant patients with radioulnar synostosis","volume":"10","author":"Shen","year":"2022","journal-title":"Mol Genet Genomic Med"},{"issue":"5","key":"10.1016\/j.gim.2025.101537_bib18","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.gim.2022.01.021","article-title":"MECOM-related disorder: radioulnar synostosis without hematological aberration due to unique variants","volume":"24","author":"Shen","year":"2022","journal-title":"Genet Med"},{"issue":"14","key":"10.1016\/j.gim.2025.101537_bib19","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"9","key":"10.1016\/j.gim.2025.101537_bib20","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res"},{"key":"10.1016\/j.gim.2025.101537_bib21","doi-asserted-by":"crossref","DOI":"10.1155\/2023\/8857940","article-title":"REVEL is better at predicting pathogenicity of loss-of-function than gain-of-function variants","volume":"2023","author":"Hopkins","year":"2023","journal-title":"Hum Mutat"},{"issue":"12","key":"10.1016\/j.gim.2025.101537_bib22","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1016\/j.ajhg.2022.10.013","article-title":"Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3\/BP4 criteria","volume":"109","author":"Pejaver","year":"2022","journal-title":"Am J Hum Genet"},{"issue":"5","key":"10.1016\/j.gim.2025.101537_bib38","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.jos.2020.12.032","article-title":"Congenital middle radioulnar synostosis: report of a probable subtype","volume":"28","author":"Yang","year":"2023","journal-title":"J Orthop Sci"},{"key":"10.1016\/j.gim.2025.101537_bib24","article-title":"Identification of novel FBN2 variants in a cohort of congenital contractural arachnodactyly","volume":"13","author":"Sun","year":"2022","journal-title":"Front Genet"},{"issue":"7616","key":"10.1016\/j.gim.2025.101537_bib25","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.gim.2025.101537_bib26","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1083\/jcb.200105046","article-title":"Regulation of limb patterning by extracellular microfibrils","volume":"154","author":"Arteaga-Solis","year":"2001","journal-title":"J Cell Biol"},{"issue":"8","key":"10.1016\/j.gim.2025.101537_bib27","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/hmg\/10.8.835","article-title":"Mutation of the gene encoding fibrillin-2 results in syndactyly in mice","volume":"10","author":"Chaudhry","year":"2001","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.gim.2025.101537_bib28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12891-016-0944-8","article-title":"Aggrecan heterogeneity in articular cartilage from patients with osteoarthritis","volume":"17","author":"Mort","year":"2016","journal-title":"BMC Musculoskelet Disord"},{"issue":"5","key":"10.1016\/j.gim.2025.101537_bib29","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.str.2009.03.014","article-title":"Structure and interdomain interactions of a hybrid domain: a disulphide-rich module of the fibrillin\/LTBP superfamily of matrix proteins","volume":"17","author":"Jensen","year":"2009","journal-title":"Structure"},{"issue":"3","key":"10.1016\/j.gim.2025.101537_bib23","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1097\/BPB.0000000000000121","article-title":"Beals-Hecht syndrome (congenital contractural arachnodactyly) with additional craniospinal abnormality: a case report","volume":"24","author":"Meena","year":"2015","journal-title":"J Pediatr Orthop B"},{"issue":"12","key":"10.1016\/j.gim.2025.101537_bib30","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1016\/j.celrep.2016.05.055","article-title":"Joint development involves a continuous influx of GDF5-positive cells","volume":"15","author":"Shwartz","year":"2016","journal-title":"Cell Rep"},{"issue":"6","key":"10.1016\/j.gim.2025.101537_bib31","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1002\/ajmg.a.33387","article-title":"Facioaudiosymphalangism syndrome and growth acceleration associated with a heterozygous NOG mutation","volume":"152A","author":"Rudnik-Sch\u00f6neborn","year":"2010","journal-title":"Am J Med Genet A"},{"issue":"11","key":"10.1016\/j.gim.2025.101537_bib32","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1002\/humu.23292","article-title":"FGF9 mutation causes craniosynostosis along with multiple synostoses","volume":"38","author":"Rodriguez-Zabala","year":"2017","journal-title":"Hum Mutat"},{"issue":"3","key":"10.1016\/j.gim.2025.101537_bib33","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/MCD.0000000000000043","article-title":"Identification of a novel familial FGF16 mutation in metacarpal 4-5 fusion","volume":"23","author":"Jones","year":"2014","journal-title":"Clin Dysmorphol"},{"issue":"5368","key":"10.1016\/j.gim.2025.101537_bib34","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1126\/science.280.5368.1455","article-title":"Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton","volume":"280","author":"Brunet","year":"1998","journal-title":"Science"},{"issue":"69","key":"10.1016\/j.gim.2025.101537_bib35","doi-asserted-by":"crossref","first-page":"113966","DOI":"10.18632\/oncotarget.23047","article-title":"Knock-in human GDF5 proregion L373R mutation as a mouse model for proximal symphalangism","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"issue":"1","key":"10.1016\/j.gim.2025.101537_bib36","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/S0012-1606(02)00022-2","article-title":"Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes","volume":"254","author":"Settle","year":"2003","journal-title":"Dev Biol"},{"issue":"7","key":"10.1016\/j.gim.2025.101537_bib37","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1093\/hmg\/ddx029","article-title":"A point mutation in FGF9 impedes joint interzone formation leading to multiple synostoses syndrome","volume":"26","author":"Tang","year":"2017","journal-title":"Hum Mol Genet"}],"container-title":["Genetics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1098360025001844?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1098360025001844?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:31:02Z","timestamp":1790825462000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1098360025001844"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["S1098360025001844"],"URL":"https:\/\/doi.org\/10.1016\/j.gim.2025.101537","relation":{},"ISSN":["1098-3600"],"issn-type":[{"value":"1098-3600","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synostosis of joints caused by mutant FBN2 is linked to the abnormalities and misdifferentiation of articular surface cells","name":"articletitle","label":"Article Title"},{"value":"Genetics in Medicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.gim.2025.101537","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 American College of Medical Genetics and Genomics. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"101537"}}