{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:30Z","timestamp":1768262430009,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Jiao Tong University School of Medicine","award":["ZH2018QNB06"],"award-info":[{"award-number":["ZH2018QNB06"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To find novel potential gene mutations other than EXT1 and EXT2 mutations, to expand the mutational spectrum of EXT and to explore the correlation between clinical outcome and genotype in patients with hereditary multiple exostoses (HME).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study recruited seven families diagnosed with multiple osteochondromas (MO). Family histories and clinical information were collected in detail through comprehensive physical and image examination. Patients with deformities and functional limitations were classified as \u201csevere\u201d and the remaining without functional limitations were classified as \u201cmild,\u201d in accordance with previous study. Whole\u2010exome sequencing (WES) was performed on a total of 13 affected individuals, 1 available unaffected relative, and 10 healthy unrelated individuals. Sanger sequencing was used to validate the screened mutations. Finally, the structural change in protein caused by pathogenic mutations was analyzed using information from the relevant database online and we attempted to correlate clinical phenotype with genotype in patients with HME.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Other than EXT1 and EXT2, no novel potential gene mutations were found through WES. We identified nine heterozygous mutations in EXT1 or EXT2. Of these mutations, four have not been reported previously. These are c.996delT in exon 2 of EXT1 (family 1), c.544C &gt; T in exon 3 of EXT2 (family 2), c.1171C &gt; T in exon 7 of EXT2 (family 5), and c.823<jats:sub>\u2013<\/jats:sub>824delAA in exon 5 of EXT1 (family 7). The other five mutations have already been reported in previous works. It was surprising that we found two mutation sites, in exon\u20092 and exon\u20095, respectively, of EXT1 in 1 patient diagnosed with MO, when his father had two mutation sites, in exon\u20096 and exon\u20095, respectively, of EXT1 and EXT2 (family 4). In addition, 1 patient showed degeneration, while his father only exhibited slight symptoms (family 7). In our study, among 51 affected patients in seven families, the sex ratio (male <jats:italic>vs<\/jats:italic> female) was 58.9% (<jats:italic>n<\/jats:italic> =\u200930) <jats:italic>vs<\/jats:italic> 41.2% (<jats:italic>n<\/jats:italic> =\u200921). Male patients seemed to show more severe symptoms compared to females, but because the sample was small, we did not obtain statistically significance results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Whole\u2010exome sequencing to screen pathogenic gene mutations was applied successfully. Although no third\u2010gene mutation associated with HME was found, a total of nine mutations across EXT1 and EXT2 were identified, four of which are novel. Our results expand the mutational spectrum of EXT and can be used in genetic counseling and prenatal diagnosis for patients with MO.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.12660","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T14:40:44Z","timestamp":1586961644000},"page":"990-996","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identification of Novel EXT Mutations in Patients with Hereditary Multiple Exostoses Using Whole\u2010Exome Sequencing"],"prefix":"10.1111","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0855-9194","authenticated-orcid":false,"given":"Chao","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong\u2010jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010xuan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital &amp; Shenzhen Hospital Chinese Academy of Sciences and Peking Union Medical College  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi\u2010chang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320550113"},{"key":"e_1_2_6_3_1","first-page":"199","article-title":"Hereditary multiple exostoses: current insights","volume":"11","author":"D'Arienzo A","year":"2019","journal-title":"Orthop Res Rev"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35819"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.J.00949"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.97"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703560200"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.668"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100296"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914642107"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2017.12.011"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21123"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.5101"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.7.1.10"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000012855"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7252"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06033-1"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2017.10.003"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-017-0488-2"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)11:3<231::AID-HUMU8>3.0.CO;2-K"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.10.1547"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-137"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.07.006"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.86B7.14815"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.311"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21423"}],"container-title":["Orthopaedic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fos.12660","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/os.12660","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/os.12660","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/os.12660","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T05:12:56Z","timestamp":1693977176000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/os.12660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1111\/os.12660"],"URL":"https:\/\/doi.org\/10.1111\/os.12660","archive":["Portico"],"relation":{},"ISSN":["1757-7853","1757-7861"],"issn-type":[{"value":"1757-7853","type":"print"},{"value":"1757-7861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,15]]},"assertion":[{"value":"2019-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}