{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T22:01:43Z","timestamp":1771106503747,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>SHOX<\/jats:italic>\n                    gene haploinsufficiency is associated with L\u00e9ri\u2010Weill dyschondrosteosis (LWD) or idiopathic short stature (ISS) and could be caused by the structural and point mutations in the coding region and by the deletions in\n                    <jats:italic>SHOX<\/jats:italic>\n                    gene regulatory sequences. The role of the duplications in regulatory sequences is ambivalent. The unanswered question is what the role of changes in\n                    <jats:italic>SHOX<\/jats:italic>\n                    gene methylation is and if they could arise as a result of\n                    <jats:italic>SHOX<\/jats:italic>\n                    area duplication. Material consisted of DNA samples from 20 LWD patients with duplication involving\n                    <jats:italic>SHOX<\/jats:italic>\n                    regulatory elements, 30 patients with LWD\/ISS phenotype without any known causal mutation in the\n                    <jats:italic>SHOX<\/jats:italic>\n                    region, and 23 healthy individuals as controls. We investigated the DNA methylation status of two CpG islands in the upstream region of the\n                    <jats:italic>SHOX<\/jats:italic>\n                    using bisulfite sequencing. Our results indicate that both CpG islands in the\n                    <jats:italic>SHOX<\/jats:italic>\n                    area show a lower level of methylation in LWD patients carrying duplications than in healthy individuals, but only one island showed a statistically significant difference. The results of methylation profiling of CpG islands in patients without any known causal mutation indicate that the methylation levels of the majority of patients differed in both CpG islands from the average of the group of healthy individuals by at least \u00b12\u2009SD. However, the biological effect of these differences will probably be clinically insignificant due to the generally very low level of methylation.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64284","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:38:27Z","timestamp":1760405907000},"page":"606-618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New Insights Into Changes in the\n                    <scp>DNA<\/scp>\n                    Methylation Pattern of the\n                    <scp>\n                      <i>SHOX<\/i>\n                    <\/scp>\n                    Gene in Patients With L\u00e9ri\u2010Weill Dyschondrosteosis"],"prefix":"10.1002","volume":"200","author":[{"given":"Valeriia","family":"Kopytko","sequence":"first","affiliation":[{"name":"Department of Anthropology and Human Genetics, Faculty of Science Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina","family":"Hirschfeldova","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Genetics, 1st Faculty of Medicine Charles University and General University Hospital  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavlina","family":"Capkova","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Olomouc University Hospital  Olomouc Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2322-6689","authenticated-orcid":false,"given":"Roman","family":"Solc","sequence":"additional","affiliation":[{"name":"Department of Anthropology and Human Genetics, Faculty of Science Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2002.01504.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-017-4110-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1689"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100678"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306685200"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014524"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37524"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35919"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43042-021-00209-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36724"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.067785"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1999.tb14404.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-1007-8"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu564"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.9.3157-3173.2002"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btad008"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018115"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/499254"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.53"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.06.034"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.03.031"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.040998"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019133"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2016-1036"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/13813450701531201"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000500468"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.26.3083"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-54"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3460"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl470"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01152"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20187"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3980"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.112680.110"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-70"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4273"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.18"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32565-1"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10716"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000455026"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32914"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36284"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25993"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt482"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.01.044"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10422"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-34639-1"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.64284","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.64284","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.64284","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T21:14:34Z","timestamp":1771103674000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.64284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,13]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/ajmg.a.64284"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.64284","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,13]]},"assertion":[{"value":"2025-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}