Runt-related transcription factor 2 (RUNX2/Cbfa1) is the main regulatory gene controlling skeletal development and morphogenesis in vertebrates. It is located on chromosome 6p21 and has two functional isoforms (type I and type II) under control of two alternate promoters (P1 and P2). Mutations within RUNX2 are linked to Cleidocranial dysplasia syndrome (CCD) in humans. CCD is an autosomal skeletal disorder characterized by several features such as delayed closure of fontanels, dental abnormalities and hypoplastic clavicles. Here, we summarize recent knowledge about RUNX2 function, mutations and their phenotypic consequences in patients.

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder linked to mutations in the Runt-related transcription factor 2, encoded by the RUNX2 gene, which is essential for osteoblast differentiation and skeletal development. Here, we describe a novel nonsense mutation (c.532C>T; p.Q178X) in RUNX2 identified in 3 affected members of a Polish family with CCD. The localization and transcriptional transactivation studies show that the mutated form of the protein has altered the subcellular localization and significantly decreased transactivation properties, respectively. Consequently, our data show that the c.532C>T mutation generates a defective RUNX2 protein and is genetically linked to the CCD phenotype.