A novel in-frame deletion of the RUNX2 gene causes a classic form of cleidocranial dysplasia

作者：Matsushita Masaki; Kitoh Hiroshi^*; Kaneko Hiroshi; Mishima Kenichi; Itoh Yasutomo; Tokita Yoshihito; Ishiguro Naoki

来源：Journal of Bone and Mineral Metabolism, 2014, 32(1): 96-99.

DOI：10.1007/s00774-013-0456-7

• Cleidocranial dysplasia
• RUNX2
• Runt domain
• PEBP2 beta
• In-frame deletion

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.Delta TLT198_200). Transcription activity of the Delta TLT198_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 Delta TLT198_200 mutation abolished the heterodimerization of the RUNX2 protein with the partner subunit, polyomavirus enhancer-binding protein 2 beta (PEBP2 beta). Destruction of RUNX2/PEBP2 beta heterodimerization activity appears to impair the function of the RUNX2 protein and cause the disease.

• 出版日期2014-1