{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T01:40:41Z","timestamp":1776044441513,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"3pt1","license":[{"start":{"date-parts":[[2013,4,25]],"date-time":"2013-04-25T00:00:00Z","timestamp":1366848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J Oral Sciences"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:p>Cleidocranial dysplasia (<jats:styled-content style=\"fixed-case\">CCD<\/jats:styled-content>) is a skeletal disorder caused by heterozygous mutations in the runt\u2010related transcription factor 2 (<jats:styled-content style=\"fixed-case\"><jats:italic>RUNX2<\/jats:italic><\/jats:styled-content>) gene. We evaluated the phenotypes of eight Chinese patients with <jats:styled-content style=\"fixed-case\">CCD<\/jats:styled-content> from three unrelated families followed by analysis of the <jats:styled-content style=\"fixed-case\"><jats:italic>RUNX2<\/jats:italic><\/jats:styled-content> genes. Three different <jats:styled-content style=\"fixed-case\"><jats:italic>RUNX2<\/jats:italic><\/jats:styled-content> frameshift mutations were identified. Two of the mutations are novel (c.887insC and c.592delA) and one (c.90insC) has been described previously. Surprisingly, the patient with the most severely truncated <jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>2 protein (c.90insC) had the mildest phenotype. The <jats:styled-content style=\"fixed-case\"><jats:italic>RUNX2<\/jats:italic><\/jats:styled-content> mutations identified were assessed for their effect on the subcellular localization of the mutant <jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>2 proteins because of previously reported inconsistent findings. All three mutant proteins showed at least partially impaired nuclear localization compared with wild\u2010type <jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>2, which was localized exclusively in the nucleus. Our findings support the notion that haploinsufficiency of <jats:styled-content style=\"fixed-case\"><jats:italic>RUNX2<\/jats:italic><\/jats:styled-content> may be mainly responsible for <jats:styled-content style=\"fixed-case\">CCD<\/jats:styled-content>. However, because the correlation between the severity of the phenotype and the degree of mutational impairment of <jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>2 is not consistent, other factors, such as nonsense\u2010mediated <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> decay and negative dominant effects, may also play a role. In addition, we show that despite the presence of the best characterized nuclear localization signal, nuclear translocation of truncated <jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>2 can be inhibited, possibly as a result of precipitation in the cytoplasm.<\/jats:p>","DOI":"10.1111\/eos.12048","type":"journal-article","created":{"date-parts":[[2013,4,25]],"date-time":"2013-04-25T13:26:41Z","timestamp":1366896401000},"page":"142-147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel <scp><i>RUNX2<\/i><\/scp> frameshift mutations in Chinese patients with cleidocranial dysplasia"],"prefix":"10.1111","volume":"121","author":[{"given":"Yanyu","family":"Huang","sequence":"first","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education School &amp; Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaling","family":"Song","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education School &amp; Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenzheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education School &amp; Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Hubei\u2010MOST KLOS &amp; KLOBM School and Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Stomatology People's Hospital of Shayang Jingmen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuan","family":"Bian","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education School &amp; Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,4,25]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"177","article-title":"Cleidocranial dysplasia: clinical and molecular genetics","volume":"36","author":"Mundlos S","year":"1999","journal-title":"J Med Genet"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/302622"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-307"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80260-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201352"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-8-82"},{"key":"e_1_2_7_8_1","first-page":"15","article-title":"Mutations in the RUNX2 gene in Chinese patients with cleidocranial dysplasia","volume":"38","author":"Xuan D","year":"2008","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/gep025"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4238\/vol9-1gmr685"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/geq044"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.12.2311"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1182\/blood.V91.5.1688","article-title":"The AML1\/ETO(MTG8) and AML1\/Evi\u20101 leukemia\u2010associated chimeric oncoproteins accumulate PEBP2beta(CBFbeta) in the nucleus more efficiently than wild\u2010type AML1","volume":"91","author":"Tanaka K","year":"1998","journal-title":"Blood"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.7.4197"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1242\/dev.126.13.2911","article-title":"Cbfa1 is required for epithelial\u2010mesenchymal interactions regulating tooth development in mice","volume":"126","author":"D'Souza RN","year":"1999","journal-title":"Development"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1079-9796(03)00020-2"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/342717"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20552"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22516"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.3.1651"}],"container-title":["European Journal of Oral Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Feos.12048","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eos.12048","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T01:31:35Z","timestamp":1700616695000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eos.12048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,25]]},"references-count":19,"journal-issue":{"issue":"3pt1","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1111\/eos.12048"],"URL":"https:\/\/doi.org\/10.1111\/eos.12048","archive":["Portico"],"relation":{},"ISSN":["0909-8836","1600-0722"],"issn-type":[{"value":"0909-8836","type":"print"},{"value":"1600-0722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,25]]},"assertion":[{"value":"2013-02-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}