Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression.

Cleidocranial dysplasia (CCD), a dominantly inherited skeletal disease, is characterized by a variable phenotype ranging from dental alterations to severe skeletal defects. Either de novo or inherited mutations in the gene have been identified in most CCD patients. Transcription factor , the osteogenic master gene, plays a central role in the commitment of mesenchymal stem cells to osteoblast lineage. With the aim to analyse the effects of mutations in CCD patients, we investigated gene expression and the osteogenic potential of two CCD patients' cells. In addition, with the aim to better understand how mutations interfere with osteogenic differentiation, we performed string analyses to identify proteins interacting with RUNX2 and analysed p53 expression levels. Our findings demonstrated for the first time that, in addition to the alteration of downstream gene expression, mutations impair p53 expression affecting osteogenic maturation. In conclusion, the present work provides new insights into the role of mutations in CCD patients and suggests that an in-depth analysis of the -associated gene network may contribute to better understand the complex molecular and phenotypic alterations in mutant subjects.