title: A novel in-frame deletion of the RUNX2 gene causes a classic form of cleidocranial dysplasia.
abstract: The runt-related transcription factor 2 (RUNX2) is a physiological regulatory gene implicated in the development of cleidocranial dysplasia (CCD). Molecular analysis of the RUNX2 gene in a 2-year-old boy with a diagnosis of CCD demonstrated a heterozygous in-frame 9-bp deletion (c.593_601delCCTTGACCA, corresponding to the amino-acid deletion p.ΔTLT198_200). Transcription activity of the ΔTLT198_200 mutant decreased in a similar degree to that of the L199F mutant, which was previously reported in the case with classic CCD. Atomic model assessment demonstrated that the ΔTLT198_200 mutation abolished the heterodimerization of the RUNX2 protein with the partner subunit, polyomavirus enhancer-binding protein 2β (PEBP2β). Destruction of RUNX2/PEBP2β heterodimerization activity appears to impair the function of the RUNX2 protein and cause the disease.
authors.affiliation: Departments of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsushita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaneko
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Itoh
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tokita
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
mesh_terms: D000818:Animals; D019556:COS Cells; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D002973:Cleidocranial Dysplasia / Q000000981:diagnostic imaging / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D006801:Humans; D008297:Male; D050505:Mutant Proteins / Q000378:metabolism; D013902:Radiography, Thoracic; D017384:Sequence Deletion / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D050505:Mutant Proteins
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