{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:00:47Z","timestamp":1784955647281,"version":"3.55.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Genet Genomics"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s00438-026-02493-1","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:12:33Z","timestamp":1784952753000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-coverage paleo-genome research identifies a pathogenic mutation on EXT1 in a Qing-period Chinese individual with multiple osteochondromas"],"prefix":"10.1007","volume":"301","author":[{"given":"Bangyan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haodong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanhao","family":"Xi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoquan","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetong","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panxin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenshuang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxue","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoshuai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-5232","authenticated-orcid":false,"given":"Chuan-Chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqing","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"2493_CR37","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","volume":"7","author":"IA Adzhubei","year":"2010","unstructured":"Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7:248\u2013249","journal-title":"Nat Methods"},{"key":"2493_CR6","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s41586-023-06618-z","volume":"625","author":"W Barrie","year":"2024","unstructured":"Barrie W, Yang Y, Irving-Pease EK, Attfield KE, Scorrano G, Jensen LT, Armen AP, Dimopoulos EA, Stern A, Refoyo-Martinez A, Pearson A, Rams\u00f8e A, Gaunitz C, Demeter F, J\u00f8rkov MLS, M\u00f8ller SB, Springborg B, Klassen L, Hyldg\u00e5rd IM, Wickmann N, Vinner L, Korneliussen TS, Allentoft ME, Sikora M, Kristiansen K, Rodriguez S, Nielsen R, Iversen AKN, Lawson DJ, Fugger L, Willerslev E (2024) Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations. Nature 625:321\u2013328","journal-title":"Nature"},{"key":"2493_CR10","first-page":"L17","volume":"24","author":"A Beckers","year":"2017","unstructured":"Beckers A, Fernandes D, Fina F, Novak M, Abati A, Rostomyan L, Thiry A, Ouafik L, Pasture B, Pinhasi R, Daly AF (2017) Paleogenetic study of ancient DNA suggestive of X-linked acrogigantism, Endocr. Relat Cancer 24:L17\u2013l20","journal-title":"Relat Cancer"},{"key":"2493_CR2","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1016\/j.cub.2023.02.041","volume":"33","author":"TJA Begg","year":"2023","unstructured":"Begg TJA, Schmidt A, Kocher A, Larmuseau MHD, Runfeldt G, Maier PA, Wilson JD, Barquera R, Maj C, Szolek A, Sager M, Clayton S, Peltzer A, Hui R, Ronge J, Reiter E, Freund C, Burri M, Aron F, Tiliakou A, Osborn J, Behar DM, Boecker M, Brandt G, Cleynen I, Strassburg C, Pr\u00fcfer K, K\u00fchnert D, Meredith WR, N\u00f6then MM, Attenborough RD, Kivisild T, Krause J (2023) Genomic analyses of hair from Ludwig van Beethoven. Curr Biol 33:1431\u20131447.e1422","journal-title":"Curr Biol"},{"key":"2493_CR15","doi-asserted-by":"crossref","unstructured":"Boer LL, Naue J, de Rooy L, Oostra RJ (2017) Detection of G1138A Mutation of the FGFR3 Gene in Tooth Material from a 180-Year-Old Museological Achondroplastic Skeleton, Genes (Basel) 8","DOI":"10.3390\/genes8090214"},{"key":"2493_CR16","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1750-1172-3-3","volume":"3","author":"JV Bov\u00e9e","year":"2008","unstructured":"Bov\u00e9e JV (2008) Multiple osteochondromas. Orphanet J Rare Dis 3:3","journal-title":"Orphanet J Rare Dis"},{"key":"2493_CR24","doi-asserted-by":"crossref","unstructured":"Caino S, Cubilla MA, Alba R, Obreg\u00f3n MG, Fano V, G\u00f3mez A, Zecchini L, Lapunzina P, Aza-Carmona M, Heath KE, Asteggiano CG (2022) Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients, Genes (Basel) 13","DOI":"10.3390\/genes13112063"},{"key":"2493_CR9","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1056\/NEJMoa1008020","volume":"364","author":"HS Chahal","year":"2011","unstructured":"Chahal HS, Stals K, Unterl\u00e4nder M, Balding DJ, Thomas MG, Kumar AV, Besser GM, Atkinson AB, Morrison PJ, Howlett TA, Levy MJ, Orme SM, Akker SA, Abel RL, Grossman AB, Burger J, Ellard S, Korbonits M (2011) AIP mutation in pituitary adenomas in the 18th century and today. N Engl J Med 364:43\u201350","journal-title":"N Engl J Med"},{"key":"2493_CR38","doi-asserted-by":"publisher","first-page":"eadg7492","DOI":"10.1126\/science.adg7492","volume":"381","author":"J Cheng","year":"2023","unstructured":"Cheng J, Novati G, Pan J, Bycroft C, \u017demgulyt\u0117 A, Applebaum T, Pritzel A, Wong LH, Zielinski M, Sargeant T, Schneider RG, Senior AW, Jumper J, Hassabis D, Kohli P, Avsec \u017d (2023) Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science 381:eadg7492","journal-title":"Science"},{"key":"2493_CR35","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","volume":"6","author":"P Cingolani","year":"2012","unstructured":"Cingolani P, Platts A, Wang le L, Coon M, Nguyen T, Wang L, Land SJ, Lu X, Ruden DM (2012) A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin) 6:80\u201392","journal-title":"Fly (Austin)"},{"key":"2493_CR7","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1126\/science.adn9644","volume":"383","author":"A Curry","year":"2024","unstructured":"Curry A (2024) Ancient DNA ties modern diseases to ancestry. Science 383:138\u2013139","journal-title":"Science"},{"key":"2493_CR33","doi-asserted-by":"publisher","first-page":"6407","DOI":"10.1038\/srep06407","volume":"4","author":"MA Delgado","year":"2014","unstructured":"Delgado MA, Martinez-Domenech G, Sarri\u00f3n P, Urreizti R, Zecchini L, Robledo HH, Segura F, de Kremer RD, Balcells S, Grinberg D, Asteggiano CG (2014) A broad spectrum of genomic changes in latinamerican patients with EXT1\/EXT2-CDG. Sci Rep 4:6407","journal-title":"Sci Rep"},{"key":"2493_CR45","doi-asserted-by":"publisher","first-page":"3996","DOI":"10.1016\/j.cub.2024.07.063","volume":"34","author":"P Du","year":"2024","unstructured":"Du P, Zhu K, Wang M, Sun Z, Tan J, Sun B, Sun B, Wang P, He G, Xiong J, Huang Z, Meng H, Sun C, Xie S, Wang B, Ge D, Ma Y, Sheng P, Ren X, Tao Y, Xu Y, Qin X, Allen E, Zhang B, Chang X, Wang K, Bao H, Yu Y, Wang L, Ma X, Du Z, Guo J, Yang X, Wang R, Ma H, Li D, Pan Y, Li B, Zhang Y, Zheng X, Han S, Jin L, Chen G, Li H, Wang CC, Wen S (2024) Genomic dynamics of the Lower Yellow River Valley since the Early Neolithic. Curr Biol 34:3996\u20134006e3911","journal-title":"Curr Biol"},{"key":"2493_CR42","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/s41586-022-05010-7","volume":"608","author":"RP Evershed","year":"2022","unstructured":"Evershed RP, Davey Smith G, Roffet-Salque M, Timpson A, Diekmann Y, Lyon MS, Cramp LJE, Casanova E, Smyth J, Whelton HL, Dunne J, Brychova V, \u0160oberl L, Gerbault P, Gillis RE, Heyd V, Johnson E, Kendall I, Manning K, Marciniak A, Outram AK, Vigne JD, Shennan S, Bevan A, Colledge S, Allason-Jones L, Amkreutz L, Anders A, Arbogast RM, B\u0103l\u0103\u015fescu A, B\u00e1nffy E, Barclay A, Behrens A, Bogucki P, Alonso C, Carretero \u00c1, Cavanagh JM, Cla\u00dfen N, Giraldo EC, Conrad H, Csengeri M, Czerniak P, D\u0119biec L, Denaire M, Dombor\u00f3czki A, Donald L, Ebert C, Evans J, Franc\u00e9s-Negro C, Gronenborn M, Haack D, Halle F, Hamon M, H\u00fclshoff C, Ilett R, Iriarte M, Jakucs E, Jeunesse J, Johnson C, Jones M, Karul AM, Kiosak N, Kotova D, Krause N, Kretschmer R, Kr\u00fcger S, Lefranc M, Lelong P, Lenneis O, Logvin E, L\u00fcth A, Marton F, Marley T, Mortimer J, Oosterbeek R, Oross L, Pav\u00fak K, Pechtl J, P\u00e9trequin J, Pollard P, Pollard J, Powlesland R, Pyzel D, Raczky J, Richardson P, Rowe A, Rowland P, Rowlandson S, Saile I, Seb\u0151k T, Schier K, Schmalfu\u00df W, Sharapova G, Sharp S, Sheridan H, Shevnina A, Sobkowiak-Tabaka I, Stadler I, St\u00e4uble P, Stobbe H, Stojanovski A, Tasi\u0107 D, van Wijk N, Vostrovsk\u00e1 I (2022) Dairying, diseases and the evolution of lactase persistence in Europe. Nature 608:336\u2013345","journal-title":"Nature"},{"key":"2493_CR47","doi-asserted-by":"publisher","first-page":"115262","DOI":"10.1016\/j.celrep.2025.115262","volume":"44","author":"H Fang","year":"2025","unstructured":"Fang H, Liang F, Ma H, Wang R, He H, Qiu L, Tao L, Zhu K, Wu W, Ma L, Zhang H, Chen S, Zhu C, Chen H, Xu Y, Zhao Y, Liu H, Wang C-C (2025) Dynamic history of the Central Plain and Haidai region inferred from Late Neolithic to Iron Age ancient human genomes. Cell Rep 44:115262","journal-title":"Cell Rep"},{"key":"2493_CR27","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1038\/s41431-021-00959-x","volume":"29","author":"I Fokkema","year":"2021","unstructured":"Fokkema I, Kroon M, L\u00f3pez Hern\u00e1ndez JA, Asscheman D, Lugtenburg I, Hoogenboom J, den Dunnen JT (2021) The LOVD3 platform: efficient genome-wide sharing of genetic variants. Eur J Hum Genet 29:1796\u20131803","journal-title":"Eur J Hum Genet"},{"key":"2493_CR3","doi-asserted-by":"publisher","first-page":"21070","DOI":"10.1038\/s41598-021-00559-1","volume":"11","author":"B Iadarola","year":"2021","unstructured":"Iadarola B, Lavezzari D, Modi A, Degli Esposti C, Beltrami C, Rossato M, Zaro V, Napione E, Latella L, Lari M, Caramelli D, Salviati A, Delledonne M (2021) Whole-exome sequencing of the mummified remains of Cangrande della Scala (1291\u20131329 CE) indicates the first known case of late-onset Pompe disease. Sci Rep 11:21070","journal-title":"Sci Rep"},{"key":"2493_CR5","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41586-023-06705-1","volume":"625","author":"EK Irving-Pease","year":"2024","unstructured":"Irving-Pease EK, Refoyo-Mart\u00ednez A, Barrie W, Ingason A, Pearson A, Fischer A, Sj\u00f6gren KG, Halgren AS, Macleod R, Demeter F, Henriksen RA, Vimala T, McColl H, Vaughn AH, Speidel L, Stern AJ, Scorrano G, Rams\u00f8e A, Schork AJ, Rosengren A, Zhao L, Kristiansen K, Iversen AKN, Fugger L, Sudmant PH, Lawson DJ, Durbin R, Korneliussen T, Werge T, Allentoft ME, Sikora M, Nielsen R, Racimo F, Willerslev E (2024) The selection landscape and genetic legacy of ancient Eurasians. Nature 625:312\u2013320","journal-title":"Nature"},{"key":"2493_CR28","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s12863-016-0359-4","volume":"17","author":"D Ishimaru","year":"2016","unstructured":"Ishimaru D, Gotoh M, Takayama S, Kosaki R, Matsumoto Y, Narimatsu H, Sato T, Kimata K, Akiyama H, Shimizu K, Matsumoto K (2016) Large-scale mutational analysis in the EXT1 and EXT2 genes for Japanese patients with multiple osteochondromas. BMC Genet 17:52","journal-title":"BMC Genet"},{"key":"2493_CR40","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1016\/j.jmb.2019.04.009","volume":"431","author":"S Ittisoponpisan","year":"2019","unstructured":"Ittisoponpisan S, Islam SA, Khanna T, Alhuzimi E, David A, Sternberg MJE (2019) Can Predicted Protein 3D Structures Provide Reliable Insights into whether Missense Variants Are Disease Associated? J Mol Biol 431:2197\u20132212","journal-title":"J Mol Biol"},{"key":"2493_CR29","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/s41431-022-01219-2","volume":"31","author":"I Jackson","year":"2023","unstructured":"Jackson I, Mattiangeli V, Cassidy LM, Murphy E, Bradley DG (2023) Millennium-old pathogenic Mendelian mutation discovery for multiple osteochondromas from a Gaelic Medieval graveyard. Eur J Hum Genet 31:248\u2013251","journal-title":"Eur J Hum Genet"},{"key":"2493_CR26","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1002\/humu.21123","volume":"30","author":"I Jennes","year":"2009","unstructured":"Jennes I, Pedrini E, Zuntini M, Mordenti M, Balkassmi S, Asteggiano CG, Casey B, Bakker B, Sangiorgi L, Wuyts W (2009) Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb). Hum Mutat 30:1620\u20131627","journal-title":"Hum Mutat"},{"key":"2493_CR20","first-page":"101505","volume":"34","author":"AG Jurik","year":"2020","unstructured":"Jurik AG (2020) Multiple hereditary exostoses and enchondromatosis, Best Pract. Res Clin Rheumatol 34:101505","journal-title":"Res Clin Rheumatol"},{"key":"2493_CR13","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3899\/jrheum.151170","volume":"43","author":"IM Laza","year":"2016","unstructured":"Laza IM, Hervella M, De-La-Rua C (2016) Genetic Markers in a Medieval Case of Ankylosing Spondylitis. J Rheumatol 43:679\u2013681","journal-title":"J Rheumatol"},{"key":"2493_CR14","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jaut.2018.07.011","volume":"94","author":"IM Laza","year":"2018","unstructured":"Laza IM, Ventades NG, Hervella M, de-la-R\u00faa C (2018) Contribution of ancient human remains analysis to the understanding of the variability in HLA-B gene variants in relation to the diagnosis of spondyloarthropathies. J Autoimmun 94:70\u201382","journal-title":"J Autoimmun"},{"key":"2493_CR12","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1136\/ard.2008.097121","volume":"68","author":"I Leden","year":"2009","unstructured":"Leden I, G\u00f6therstr\u00f6m A, Drenzel L, Svensson B (2009) HLA-B27 sequences identified in a mediaeval skeleton with ankylosing spondylitis. Ann Rheum Dis 68:757\u2013758","journal-title":"Ann Rheum Dis"},{"key":"2493_CR52","doi-asserted-by":"publisher","first-page":"7110","DOI":"10.1038\/s41467-022-34882-6","volume":"13","author":"F Leisico","year":"2022","unstructured":"Leisico F, Omeiri J, Le Narvor C, Beaudouin J, Hons M, Fenel D, Schoehn G, Cout\u00e9 Y, Bonnaff\u00e9 D, Sadir R, Lortat-Jacob H, Wild R (2022) Structure of the human heparan sulfate polymerase complex EXT1-EXT2. Nat Commun 13:7110","journal-title":"Nat Commun"},{"key":"2493_CR49","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12881-017-0488-2","volume":"18","author":"Y Li","year":"2017","unstructured":"Li Y, Wang J, Wang Z, Tang J, Yu T (2017) A genotype-phenotype study of hereditary multiple exostoses in forty-six Chinese patients. BMC Med Genet 18:126","journal-title":"BMC Med Genet"},{"key":"2493_CR50","doi-asserted-by":"publisher","first-page":"e12855","DOI":"10.1097\/MD.0000000000012855","volume":"97","author":"Y Li","year":"2018","unstructured":"Li Y, Wang J, Tang J, Wang Z, Han B, Li N, Yu T, Chen Y, Fu Q (2018) Heterogeneous spectrum of EXT gene mutations in Chinese patients with hereditary multiple osteochondromas. Med 97:e12855","journal-title":"Med"},{"key":"2493_CR32","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/s41589-022-01220-2","volume":"19","author":"H Li","year":"2023","unstructured":"Li H, Chapla D, Amos RA, Ramiah A, Moremen KW, Li H (2023) Structural basis for heparan sulfate co-polymerase action by the EXT1-2 complex. Nat Chem Biol 19:565\u2013574","journal-title":"Nat Chem Biol"},{"key":"2493_CR44","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1038\/s41467-025-56555-w","volume":"16","author":"J Liu","year":"2025","unstructured":"Liu J, Liu Y, Zhao Y, Zhu C, Wang T, Zeng W, Sun B, Wang F, Han H, Li Z, Feng X, Cao P, Luan F, Liu F, Dai Q, Guo J, Wang Z, Wei C, Wei Q, Yang R, Hou W, Ping W, Bai F, Miao B, Wang W, Yang MA, Fu Q (2025) East Asian Gene flow bridged by northern coastal populations over past 6000 years. Nat Commun 16:1322","journal-title":"Nat Commun"},{"key":"2493_CR21","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1002\/oa.1390030402","volume":"3","author":"H Lyall","year":"1993","unstructured":"Lyall H, Mann GE (1993) Diaphyseal aclasis in citizens of ancient Jericho. Int J Osteoarchaeology 3:233\u2013240","journal-title":"Int J Osteoarchaeology"},{"key":"2493_CR11","doi-asserted-by":"crossref","unstructured":"Haak W, Gruber P, R\u00fchli FJ, B\u00f6ni T, Ulrich-Bochsler S, Frauendorf E, Burger J, Alt KW (2005) Molecular evidence of HLA\u2013B27 in a historical case of ankylosing spondylitis. Arthritis Rheum. 52","DOI":"10.1002\/art.21371"},{"key":"2493_CR8","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.ijpp.2021.04.009","volume":"33","author":"F Maixner","year":"2021","unstructured":"Maixner F, Gresky J, Zink A (2021) Ancient DNA analysis of rare genetic bone disorders. Int J Paleopathol 33:182\u2013187","journal-title":"Int J Paleopathol"},{"key":"2493_CR17","doi-asserted-by":"crossref","unstructured":"Michaeli O, Kim SY, Mitchell SG, Jongmans MCJ, Wasserman JD, Perrino MR, Das A, MacFarland SP, Scollon SR, Greer MC, Sobreira N, Gallinger B, Lupo PJ, Malkin D, Schneider KW, Schultz KAP, Foulkes WD, Woodward ER, Stewart DR (2024) Update on cancer screening in children with syndromes of bone lesions, hereditary leiomyoma and renal cell carcinoma syndrome, and other rare syndromes, Clin. Cancer Res.","DOI":"10.1158\/1078-0432.CCR-24-2171"},{"key":"2493_CR36","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1101\/gr.176601","volume":"11","author":"PC Ng","year":"2001","unstructured":"Ng PC, Henikoff S (2001) Predicting deleterious amino acid substitutions. Genome Res 11:863\u2013874","journal-title":"Genome Res"},{"key":"2493_CR19","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1007\/s11914-017-0355-2","volume":"15","author":"M Pacifici","year":"2017","unstructured":"Pacifici M (2017) Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments. Curr Osteoporos Rep 15:142\u2013152","journal-title":"Curr Osteoporos Rep"},{"key":"2493_CR25","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.matbio.2017.12.011","volume":"71\u201372","author":"M Pacifici","year":"2018","unstructured":"Pacifici M (2018) The pathogenic roles of heparan sulfate deficiency in hereditary multiple exostoses. Matrix Biol 71\u201372:28\u201339","journal-title":"Matrix Biol"},{"key":"2493_CR4","doi-asserted-by":"crossref","unstructured":"Patin E, Quintana-Murci L (2024) Tracing the Evolution of Human Immunity Through Ancient DNA. Annu Rev Immunol","DOI":"10.1146\/annurev-immunol-082323-024638"},{"key":"2493_CR31","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1016\/j.ajhg.2022.10.013","volume":"109","author":"V Pejaver","year":"2022","unstructured":"Pejaver V, Byrne AB, Feng BJ, Pagel KA, Mooney SD, Karchin R, O\u2019Donnell-Luria A, Harrison SM, Tavtigian SV, Greenblatt MS, Biesecker LG, Radivojac P, Brenner SE (2022) Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3\/BP4 criteria. Am J Hum Genet 109:2163\u20132177","journal-title":"Am J Hum Genet"},{"key":"2493_CR39","doi-asserted-by":"crossref","unstructured":"Powell HR, Islam SA, David A, Sternberg MJE (2025) Phyre2.2: A Community Resource for Template-based Protein Structure Prediction. J Mol Biol, 168960","DOI":"10.1016\/j.jmb.2025.168960"},{"key":"2493_CR41","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405\u2013424","journal-title":"Genet Med"},{"key":"2493_CR53","doi-asserted-by":"crossref","unstructured":"Ringbauer H, Huang Y, Akbari A, Mallick S, Olalde I, Patterson N, Reich D (2023) Accurate detection of identity-by-descent segments in human ancient DNA. Nat Genet","DOI":"10.1101\/2023.03.08.531671"},{"key":"2493_CR1","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1038\/s41467-024-45438-1","volume":"15","author":"AB Rohrlach","year":"2024","unstructured":"Rohrlach AB, Rivollat M, de-Miguel-Ib\u00e1\u00f1ez P, Moilanen U, Liira AM, Teixeira JC, Roca-Rada X, Armend\u00e1riz-Martija J, Boyadzhiev K, Boyadzhiev Y, Llamas B, Tiliakou A, M\u00f6tsch A, Tuke J, Prevedorou EA, Polychronakou-Sgouritsa N, Buikstra J, Onkamo P, Stockhammer PW, Heyne HO, Lemke JR, Risch R, Schiffels S, Krause J, Haak W, Pr\u00fcfer K (2024) Cases of trisomy 21 and trisomy 18 among historic and prehistoric individuals discovered from ancient DNA. Nat Commun 15:1294","journal-title":"Nat Commun"},{"key":"2493_CR34","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1002\/mgg3.382","volume":"6","author":"SCL Santos","year":"2018","unstructured":"Santos SCL, Rizzo I, Takata RI, Speck-Martins CE, Brum JM, Sollaci C (2018) Analysis of mutations in EXT1 and EXT2 in Brazilian patients with multiple osteochondromas. Mol Genet Genomic Med 6:382\u2013392","journal-title":"Mol Genet Genomic Med"},{"key":"2493_CR30","doi-asserted-by":"publisher","first-page":"D1143","DOI":"10.1093\/nar\/gkad989","volume":"52","author":"M Schubach","year":"2024","unstructured":"Schubach M, Maass T, Nazaretyan L, R\u00f6ner S, Kircher M (2024) CADD v1.7: using protein language models, regulatory CNNs and other nucleotide-level scores to improve genome-wide variant predictions. Nucleic Acids Res 52:D1143\u2013d1154","journal-title":"Nucleic Acids Res"},{"key":"2493_CR46","doi-asserted-by":"crossref","unstructured":"Shen Q, Wu Z, Zan J, Yang X, Guo J, Ji Z, Wang B, Liu Y, Mao X, Wang X, Zou X, Zhou H, Peng Y, Ma H, He H, Bai T, Xu M, Wen S, Jin L, Zhang Q, Wang CC (2024) Ancient genomes illuminate the demographic history of Shandong over the past two millennia, J Genet Genomics.","DOI":"10.1016\/j.jgg.2024.07.008"},{"key":"2493_CR18","doi-asserted-by":"publisher","first-page":"110","DOI":"10.5435\/00124635-200503000-00004","volume":"13","author":"JR Stieber","year":"2005","unstructured":"Stieber JR, Dormans JP (2005) Manifestations of hereditary multiple exostoses. J Am Acad Orthop Surg 13:110\u2013120","journal-title":"J Am Acad Orthop Surg"},{"key":"2493_CR51","doi-asserted-by":"publisher","first-page":"607838","DOI":"10.3389\/fgene.2020.607838","volume":"11","author":"Y Wang","year":"2020","unstructured":"Wang Y, Zhong L, Xu Y, Ding L, Ji Y, Schutz S, F\u00e9rec C, Cooper DN, Xu C, Chen JM, Luo Y (2020) EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis. Front Genet 11:607838","journal-title":"Front Genet"},{"key":"2493_CR43","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.scib.2023.12.031","volume":"69","author":"J Xiong","year":"2024","unstructured":"Xiong J, Wang R, Chen G, Yang Y, Du P, Meng H, Ma M, Allen E, Tao L, Wang H, Jin L, Wang CC, Wen S (2024) Inferring the demographic history of Hexi Corridor over the past two millennia from ancient genomes. Sci Bull (Beijing) 69:606\u2013611","journal-title":"Sci Bull (Beijing)"},{"key":"2493_CR48","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s004399900058","volume":"105","author":"L Xu","year":"1999","unstructured":"Xu L, Xia J, Jiang H, Zhou J, Li H, Wang D, Pan Q, Long Z, Fan C, Deng HX (1999) Mutation analysis of hereditary multiple exostoses in the Chinese. Hum Genet 105:45\u201350","journal-title":"Hum Genet"},{"key":"2493_CR23","first-page":"105","volume":"5","author":"XY Zhang","year":"2025","unstructured":"Zhang XY, Yan X, Wang MH, Zhang X, Hu YW (2025) Marine reservoir effect on the carbon 14 dating of human skeletons from coastal regions: case study of the Dakou Site on Tuoji Island, Shandong. Archaeology 5:105\u2013122","journal-title":"Archaeology"},{"key":"2493_CR22","doi-asserted-by":"crossref","unstructured":"Zhou YW, Xi FH, Zhao FC, Berger E (2024) A probable case of multiple osteochondromas in a Qing period (1644\u20131911) individual from Shandong, China. International Journal of Osteoarchaeology","DOI":"10.1002\/oa.3323"}],"container-title":["Molecular Genetics and Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00438-026-02493-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00438-026-02493-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00438-026-02493-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:12:35Z","timestamp":1784952755000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00438-026-02493-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,25]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["2493"],"URL":"https:\/\/doi.org\/10.1007\/s00438-026-02493-1","relation":{},"ISSN":["1617-4615","1617-4623"],"issn-type":[{"value":"1617-4615","type":"print"},{"value":"1617-4623","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,25]]},"assertion":[{"value":"5 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"161"}}