Diversity of supernumerary tooth formation in siblings with cleidocranial dysplasia having identical mutation in RUNX2 : possible involvement of non-genetic or epigenetic regulation.
Overall, these results suggest that CCD could result from a much smaller loss in the RUNX2 function than envisioned on the basis of the conventional haploinsufficiency model.
Chromosomal translocations, deletions, insertions, nonsense and splice-site mutations, as well as missense mutations of the RUNX2 gene have been described in CCD patients.
On the one hand, these genotype-phenotype correlations highlight a general, quantitative dependency, by skeleto-dental developments, on the gene dosage of RUNX2, which has hitherto been obscured by extreme clinical diversities of CCD; this gene-dosage effect is presumed to manifest on small reductions in the total RUNX2 activity, by approximately one-fourth of the normal level at minimum.