{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:17:39Z","timestamp":1740104259602,"version":"3.37.3"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Federal Target Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2024,2,12]]},"abstract":"<jats:p>This study is aimed at investigating the clinical and genetic characteristics of 244 unrelated probands diagnosed with multiple osteochondromas (MO). The diagnosis of MO typically involves identifying multiple benign bone tumors known as osteochondromas (OCs) through imaging studies and physical examinations. However, cases with both OCs and enchondromas (ECs) may indicate the more rare condition metachondromatosis (MC), which is assumed to be distinct disease. Previous cohort studies of MO found heterozygous loss-of-function (LoF) variants only in the EXT1 or EXT2 genes, with DNA diagnostic yield ranging from 78 to 95%. The PTPN11 gene, which is causative for MC, was not previously investigated as a gene candidate for MO. In this study, we detected a total of 177 unique single nucleotide and copy number variants in three genes across 220 probands, consisting of 80 previously reported and 97 novel variants. Specifically, we identified five cases with OCs and no ECs as well as four cases with MC carrying LoF variants in the PTPN11 gene and two additional cases with ECs harboring variants in the EXT1\/2 genes. These findings suggest a potential overlap between the MO and MC both phenotypically and genetically. These findings highlight the importance of expanding genetic testing beyond the EXT1 and EXT2 genes in MO cases, as other genes such as PTPN11 may also be causative. This can improve the accuracy of diagnosis and treatment for individuals with MO and MC. It is essential to determine whether MO and MC represent distinct diseases or if they encompass a broader clinical spectrum.<\/jats:p>","DOI":"10.1155\/2024\/8849348","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T19:20:05Z","timestamp":1707765605000},"page":"1-13","source":"Crossref","is-referenced-by-count":1,"title":["The Missing Piece of the Puzzle: Unveiling the Role of PTPN11 Gene in Multiple Osteochondromas in a Large Cohort Study"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-8005","authenticated-orcid":true,"given":"Artem","family":"Borovikov","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-7283","authenticated-orcid":true,"given":"Nailya","family":"Galeeva","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-5118","authenticated-orcid":true,"given":"Andrey","family":"Marakhonov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7023-7378","authenticated-orcid":true,"given":"Aysylu","family":"Murtazina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1245-4881","authenticated-orcid":true,"given":"Varvara","family":"Kadnikova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7620-9175","authenticated-orcid":true,"given":"Kseniya","family":"Davydenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8831-1844","authenticated-orcid":true,"given":"Anna","family":"Orlova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9160-0794","authenticated-orcid":true,"given":"Peter","family":"Sparber","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2672-6294","authenticated-orcid":true,"given":"Tatiana","family":"Markova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3743-094X","authenticated-orcid":true,"given":"Maria","family":"Orlova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5863-3543","authenticated-orcid":true,"given":"Darya","family":"Osipova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4527-4518","authenticated-orcid":true,"given":"Tatyana","family":"Nagornova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-045X","authenticated-orcid":true,"given":"Natalia","family":"Semenova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9465-4213","authenticated-orcid":true,"given":"Olga","family":"Levchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5979-0727","authenticated-orcid":true,"given":"Alexandra","family":"Filatova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3148-6915","authenticated-orcid":true,"given":"Margarita","family":"Sharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8249-343X","authenticated-orcid":true,"given":"Peter","family":"Vasiluev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5821-9783","authenticated-orcid":true,"given":"Ilya","family":"Kanivets","sequence":"additional","affiliation":[{"name":"Genomed, Moscow, Russia"},{"name":"Russian Medical Academy of Continuous Professional Education, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2519-4908","authenticated-orcid":true,"given":"Denis","family":"Pyankov","sequence":"additional","affiliation":[{"name":"Genomed, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-2638","authenticated-orcid":true,"given":"Artem","family":"Sharkov","sequence":"additional","affiliation":[{"name":"Genomed, Moscow, Russia"},{"name":"Veltischev Research and Clinical Institute of Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3476-2225","authenticated-orcid":true,"given":"Vasilisa","family":"Udalova","sequence":"additional","affiliation":[{"name":"Genomed, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7651-8485","authenticated-orcid":true,"given":"Vladimir","family":"Kenis","sequence":"additional","affiliation":[{"name":"The Turner Scientific Research Institute for Children\u2019s Orthopedics, Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2811-4718","authenticated-orcid":true,"given":"Natalia","family":"Nikitina","sequence":"additional","affiliation":[{"name":"State Healthcare Institution of Sverdlovsk Region \u201cClinical and Diagnostic Center \u201cMother\u2019s and Child Health Protection\u201d, Ekaterinburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-4029","authenticated-orcid":true,"given":"Maria","family":"Sumina","sequence":"additional","affiliation":[{"name":"State Healthcare Institution of Sverdlovsk Region \u201cClinical and Diagnostic Center \u201cMother\u2019s and Child Health Protection\u201d, Ekaterinburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-6011","authenticated-orcid":true,"given":"Konstantin","family":"Zherdev","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Children\u2019s Health, Moscow, Russia"},{"name":"I.M. Sechenov First Moscow State Medical University, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6686-4042","authenticated-orcid":true,"given":"Aleksandr","family":"Petel'guzov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Children\u2019s Health, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0333-3105","authenticated-orcid":true,"given":"Oleg","family":"Chelpachenko","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Children\u2019s Health, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9408-8004","authenticated-orcid":true,"given":"Pavel","family":"Zubkov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Children\u2019s Health, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7508-6185","authenticated-orcid":true,"given":"Ivan","family":"Dan","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Traumatology and Orthopedics Named after N.N. Priorov, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2435-6920","authenticated-orcid":true,"given":"Andrey","family":"Snetkov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Traumatology and Orthopedics Named after N.N. Priorov, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7319-5350","authenticated-orcid":true,"given":"Alexandra","family":"Akinshina","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Traumatology and Orthopedics Named after N.N. Priorov, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0039-2118","authenticated-orcid":true,"given":"Yury","family":"Buklemishev","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Traumatology and Orthopedics Named after N.N. Priorov, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-9093","authenticated-orcid":true,"given":"Oxana","family":"Ryzhkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0291-153X","authenticated-orcid":true,"given":"Vyacheslav","family":"Tabakov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5020-1180","authenticated-orcid":true,"given":"Ekaterina","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3816-8031","authenticated-orcid":true,"given":"Sergey","family":"Korostelev","sequence":"additional","affiliation":[{"name":"Genomed, Moscow, Russia"},{"name":"I.M. Sechenov First Moscow State Medical University, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-3458","authenticated-orcid":true,"given":"Rena","family":"Zinchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7293-3438","authenticated-orcid":true,"given":"Mikhail","family":"Skoblov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0105-1833","authenticated-orcid":true,"given":"Alexander","family":"Polyakov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5602-2805","authenticated-orcid":true,"given":"Elena","family":"Dadali","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3133-8018","authenticated-orcid":true,"given":"Sergey","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4905-1303","authenticated-orcid":true,"given":"Olga","family":"Shchagina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-137"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0996-25"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-3-3"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01219-2"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/514"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0065"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2613.2008.00589.x"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100296"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10635"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0169(200102)48:2<149::AID-CM1005>3.0.CO;2-3"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20625"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.287"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9467"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21423"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1186\/s12863-016-0359-4"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000012855"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.382"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.3390\/genes13112063"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-014-0195-z"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1038\/srep01346"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10212"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21162"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094848"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.5.717"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000991"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002050"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn336"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1038\/ng772"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1038\/nature12396"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2062"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1007\/s11832-013-0526-3"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35819"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62470"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-018-0326-1"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz046"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.11.055"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34882-6"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01220-2"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9314-8"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-12-85"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.N.00121"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-021-03967-6"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.CC.15.00182"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2004.09.025"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.12.003"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.J.00949"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200208000-00008"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2219"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103279"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/humu\/2024\/8849348.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/humu\/2024\/8849348.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/humu\/2024\/8849348.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T19:20:09Z","timestamp":1707765609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/humu\/2024\/8849348\/"}},"subtitle":[],"editor":[{"given":"Stuart","family":"Scott","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,12]]},"references-count":51,"alternative-id":["8849348","8849348"],"URL":"https:\/\/doi.org\/10.1155\/2024\/8849348","relation":{},"ISSN":["1098-1004","1059-7794"],"issn-type":[{"type":"electronic","value":"1098-1004"},{"type":"print","value":"1059-7794"}],"subject":[],"published":{"date-parts":[[2024,2,12]]}}}