{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:00Z","timestamp":1772160060614,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005632","name":"Narodowe Centrum Bada\u0144 i Rozwoju","doi-asserted-by":"publisher","award":["LIDER\/008\/431\/L\u20104\/12\/NCBR\/2013 to AJ"],"award-info":[{"award-number":["LIDER\/008\/431\/L\u20104\/12\/NCBR\/2013 to AJ"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO\u20102013\/11\/B\/NZ4\/03660 to PT"],"award-info":[{"award-number":["UMO\u20102013\/11\/B\/NZ4\/03660 to PT"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO\u20102016\/22\/E\/NZ5\/00270 to AJ"],"award-info":[{"award-number":["UMO\u20102016\/22\/E\/NZ5\/00270 to AJ"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO2016\/23\/N\/NZ5\/02577 to EO"],"award-info":[{"award-number":["UMO2016\/23\/N\/NZ5\/02577 to EO"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    RUNX2 (Runt\u2010related transcription factor 2) is a master regulator of osteoblast differentiation, cartilage and bone development. Pathogenic variants in\n                    <jats:italic>RUNX2<\/jats:italic>\n                    have been linked to the Cleidocranial dysplasia (CCD), which is characterized by hypoplasia or aplasia of clavicles, delayed fontanelle closure, and dental anomalies. Here, we report 11 unrelated Polish patients with CCD caused by pathogenic alterations located in the Runt domain of\n                    <jats:italic>RUNX2<\/jats:italic>\n                    . In total, we identified eight different intragenic variants, including seven missense and one splicing mutation. Three of them are novel: c.407T&gt;A p.(Leu136Gln), c.480C&gt;G p.(Asn160Lys), c.659C&gt;G p.(Thr220Arg), additional three were not functionally tested: c.391C&gt;T p.(Arg131Cys), c.580+1G&gt;T p.(Lys195_Arg229del), c.652A&gt;G p.(Lys218Glu), and the remaining two: c.568C&gt;T p.(Arg190Trp), c.673C&gt;T p.(Arg225Trp) were previously reported and characterized. The performed transactivation and localization studies provide evidence of decreased transcriptional activity of RUNX2 due to mutations targeting the Runt domain and prove that impairment of nuclear localization signal (NLS) affects the subcellular localization of the protein. Presented data show that pathogenic variants discovered in our patients have a detrimental effect on RUNX2, triggering the CCD phenotype.\n                  <\/jats:p>","DOI":"10.1111\/cge.13610","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T03:44:32Z","timestamp":1564112672000},"page":"429-438","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Functional analysis of novel\n                    <i>RUNX2<\/i>\n                    mutations identified in patients with cleidocranial dysplasia"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4544-1240","authenticated-orcid":false,"given":"Ewa","family":"Hordyjewska\u2010Kowalczyk","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical University  Lublin Poland"},{"name":"The Postgraduate School of Molecular Medicine Medical University of Warsaw  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Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kruczek","sequence":"additional","affiliation":[{"name":"Genetic Counseling Unit Kostyk and Kruczek  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Latos\u2010Biele\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Poznan University of Medical Sciences  Pozna\u0144 Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Przemko","family":"Tylzanowski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical University  Lublin Poland"},{"name":"Laboratory for Developmental and Stem Cell Biology, Department of Development and Regeneration Skeletal Biology and Engineering Research Centre, University of Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksander","family":"Jamsheer","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Poznan University of Medical Sciences  Pozna\u0144 Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-307"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601568"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80260-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12812"},{"key":"e_1_2_8_6_1","first-page":"212","article-title":"Histological observations of teeth and peridental tissues in cleidocranial dysplasia imply increased activity of odontogenic epithelium and abnormal bone remodeling","volume":"15","author":"Lukinmaa 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