{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T21:58:45Z","timestamp":1772143125919,"version":"3.50.1"},"reference-count":17,"publisher":"Elsevier BV","issue":"01","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glob Med Genet"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003Cleidocranial dysplasia (CCD, #MIM119600) is an autosomal-dominant skeletal dysplasia characterized by delayed closure of the cranial sutures, aplasia, or hypoplasia of the clavicles and dental abnormalities. These findings were accompanied by mobile and drooping shoulders, frontal and parietal bossing, hypertelorism, brachycephaly, short stature, supernumerary, and late erupting teeth. Radiographic studies can reveal involvement of multiple bones including skull, chest, pelvis, and limbs. CCD can be diagnosed with clinical and radiological evaluation and validated by molecular studies. Heterozygous loss of function RUNX2 gene, which plays an important role in osteogenesis and differentiation of precursor cells, causes CCD phenotype.<\/jats:p><jats:p>\n          Methods\u2003In this article, we reported five cases from three unrelated families with CCD phenotype. All exons and exonic\u2013intronic boundary regions of RUNX2 gene from five patients were analyzed by polymerase chain reaction amplification and direct Sanger-sequencing.<\/jats:p><jats:p>\n          Results\u2003Our patients had classical CCD phenotype and we detected three different previously described mutations including c.1171C\u2009&gt;\u2009T, IVS4\u2009+\u20094delAAGT and c.676G\u2009&gt;\u2009A. However, nail dysplasia has never been associated with these mutations. Our patients had varying degrees of nail dysplasia. Two of three mutations are related with Runt DNA-binding domain of RUNX2 protein in Wnt signaling and c.1171C\u2009&gt;\u2009T had effect on proline\/serine\/threonine-rich (PST) domain. Recently, Wnt signaling pathway was presented as a key regulator of digit and nail differentiation. Our data suggest that RUNX2 gene may have an essential role on embryogenesis of nails, probably by protecting their integrity.<\/jats:p>","DOI":"10.1055\/s-0041-1736482","type":"journal-article","created":{"date-parts":[[2021,10,23]],"date-time":"2021-10-23T03:26:15Z","timestamp":1634959575000},"page":"023-028","source":"Crossref","is-referenced-by-count":3,"title":["Rare Findings in Cleidocranial Dysplasia Caused by RUNX Mutation"],"prefix":"10.1016","volume":"09","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8549-5564","authenticated-orcid":false,"given":"Aysel","family":"Kalayci Yigin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul University-Cerrahpa\u015fa, Cerrahpa\u015fa Medical School, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2140-5456","authenticated-orcid":false,"given":"Mehmet Bugrahan","family":"Duz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Health Sciences University, Haseki Training and Research Hospital, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7878-2039","authenticated-orcid":false,"given":"Mehmet","family":"Seven","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul University-Cerrahpa\u015fa, Cerrahpa\u015fa Medical School, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"ref1","first-page":"1993","volume-title":"Cleidocranial dysplasia spectrum disorder","author":"K Machol"},{"issue":"05","key":"ref2","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1002\/ajmg.a.35327","article-title":"Analysis of skeletal dysplasias in the Utah population","volume":"158A","author":"D A Stevenson","year":"2012","journal-title":"Am J Med Genet A"},{"issue":"02","key":"ref3","first-page":"529","article-title":"Cleidocranial dysplasia: maxillary alterations on the transverse plane. Presence of crown-radicular anomalies and multidisciplinary approach of a clinical case","volume":"13","author":"U Romeo","year":"2014","journal-title":"Oral Health Dent Manag"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1752-1947-6-25","article-title":"Cleidocranial dysplasia presenting with retained deciduous teeth in a 15-year-old girl: a case report","volume":"6","author":"C Nagarathna","year":"2012","journal-title":"J Med Case Reports"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1259\/dmfr\/63490079","article-title":"Dentomaxillofacial variability of cleidocranial dysplasia: clinicoradiological presentation and systematic review","volume":"32","author":"I Golan","year":"2003","journal-title":"Dentomaxillofac Radiol"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/SCS.0b013e3182636b7e","article-title":"Biology of RUNX2 and cleidocranial dysplasia","volume":"24","author":"M M Cohen Jr","year":"2013","journal-title":"J Craniofac Surg"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.bone.2015.02.009","article-title":"Wnt signaling in bone and muscle","volume":"80","author":"M A Rudnicki","year":"2015","journal-title":"Bone"},{"issue":"39","key":"ref8","doi-asserted-by":"crossref","first-page":"33132","DOI":"10.1074\/jbc.M500608200","article-title":"Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression","volume":"280","author":"T Gaur","year":"2005","journal-title":"J Biol Chem"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nature12214","article-title":"Wnt activation in nail epithelium couples nail growth to digit regeneration","volume":"499","author":"M Takeo","year":"2013","journal-title":"Nature"},{"issue":"02","key":"ref10","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/bdra.20231","article-title":"Cleidocranial dysplasia with severe parietal bone dysplasia: C-terminal RUNX2 mutations","volume":"76","author":"M L Cunningham","year":"2006","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"issue":"09","key":"ref11","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1097\/00005537-200309000-00017","article-title":"Otolaryngological manifestations of cleidocranial dysplasia, concentrating on audiological findings","volume":"113","author":"A M Visosky","year":"2003","journal-title":"Laryngoscope"},{"issue":"01","key":"ref12","first-page":"1057","article-title":"Novel mutation of RUNX2 gene in a patient with cleidocranial dysplasia","volume":"8","author":"Y W Guo","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"issue":"03","key":"ref13","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/humu.10043","article-title":"Mutations in the RUNX2 gene in patients with cleidocranial dysplasia","volume":"19","author":"F Otto","year":"2002","journal-title":"Hum Mutat"},{"issue":"08","key":"ref14","doi-asserted-by":"crossref","first-page":"E1587","DOI":"10.1002\/humu.21298","article-title":"Deletions of the RUNX2 gene are present in about 10% of individuals with cleidocranial dysplasia","volume":"31","author":"C E Ott","year":"2010","journal-title":"Hum Mutat"},{"issue":"03","key":"ref15","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/j.1399-0004.2010.01458.x","article-title":"RUNX2 analysis of Danish cleidocranial dysplasia families","volume":"79","author":"L Hansen","year":"2011","journal-title":"Clin Genet"},{"issue":"02","key":"ref16","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/ajmg.a.30927","article-title":"Cleidocranial dysplasia: molecular genetic analysis and phenotypic-based description of a Middle European patient group","volume":"139A","author":"U Baumert","year":"2005","journal-title":"Am J Med Genet A"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1471-2350-8-82","article-title":"A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails","volume":"8","author":"S Tang","year":"2007","journal-title":"BMC Med Genet"}],"container-title":["Global Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0041-1736482.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T15:22:49Z","timestamp":1736436169000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1736482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":17,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2022,2,11]]},"published-print":{"date-parts":[[2022,3]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0041-1736482","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2699-9404"],"issn-type":[{"value":"2699-9404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]}}}