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Clinical features of CCD comprise short stature, delayed ossification of craniofacial structures with numerous Wormian bones, underdeveloped or aplastic clavicles and multiple dental anomalies. Several studies have revealed that CCD development is strongly linked with different mutations in runt-related transcription factor 2 (<jats:italic>RUNX2<\/jats:italic>) gene.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>Identification and functional characterization of <jats:italic>RUNX2<\/jats:italic> mutation associated with CCD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed genetic testing of a patient with CCD using whole exome sequencing and found a novel <jats:italic>RUNX2<\/jats:italic> frameshift mutation: c.1550delT in a sporadic case. We also compared the functional activity of the mutant and wild-type <jats:italic>RUNX2<\/jats:italic> through immunofluorescence microscopy and osteocalcin promoter luciferase assay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found a novel <jats:italic>RUNX2<\/jats:italic> frameshift mutation, c.1550delT (p.Trp518Glyfs*60). Both mutant <jats:italic>RUNX2<\/jats:italic> and wild-type <jats:italic>RUNX2<\/jats:italic> protein were similarly confined in the nuclei. The novel mutation caused abrogative transactivation activity of <jats:italic>RUNX2<\/jats:italic> on osteocalcin promoter.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We explored a novel <jats:italic>RUNX2<\/jats:italic> deletion\/frameshift mutation in a sporadic CCD patient. This finding suggests that the VWRPY domain may play a key role in <jats:italic>RUNX2<\/jats:italic> transactivation ability.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s13258-022-01229-w","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T05:03:23Z","timestamp":1646197403000},"page":"683-690","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification a novel de novo RUNX2 frameshift mutation associated with cleidocranial dysplasia"],"prefix":"10.1007","volume":"44","author":[{"given":"Lei","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekzod","family":"Odilov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinguo","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"1229_CR1","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1097\/SCS.0000000000004200","volume":"29","author":"E Farrow","year":"2018","unstructured":"Farrow E, Nicot R, Wiss A, Laborde A, Ferri J (2018) Cleidocranial dysplasia: a review of clinical, radiological, genetic implications and a guidelines proposal. 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Prior to genotyping and analysis, all samples were stripped of personal identifiers (if any existed).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}