Novel Mutation of Cleidocranial Dysplasia-related Frameshift Runt-related Transcription Factor 2 in a Sporadic Chinese Case

Background: Cleidocranial dysplasia (CCD) is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 (RUNX2). Here, we report a sporadic Chinese case presenting typical symptoms of CCD.Methods: We made genetic testing on this sporadic Chinese case and identified a novelRUNX2 frameshift mutation: c.1111dupT.In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of theRUNX2 mutation with those of wild-typeRUNX2.Results: RUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-typeRUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization ofRUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of theRUNX2 mutation was obviously abrogated.Conclusions: We identified a sporadic CCD patient carrying a novel insertion/frameshift mutation ofRUNX2. This finding expanded our understanding of CCD-related phenotypes.