Evidence of intrafamilial variability of CBFA1/RUNX2 expression in cleidocranial dysplasia--a family study

Aim: To investigate the phenotypical expression of an identical mutation of the CBFA1/RUNX2 gene within a family with cleidocranial dysplasia. Patients and Method: A five-member family underwent clinical examination.Two members, father and son, showed dissimilar symptoms of cleidocranial dysplasia. The two affected patients were examined for syndrome-typical symptoms, and the genotype was determined by molecular-genetic analysis. Results: In both patients an identical missense mutation (G146R) in exon 2 of the CBFA1/RUNX2 gene was identified. In father and son the dental disturbances were similarly clearly expressed. However, the craniofacial skeleton of the son exhibited fewer dysostotic ossification features than that of the father. In the three clinically healthy family-members no mutation of the CBFA1/RUNX2 gene was found. Conclusion: In two patients with cleidocranial dysplasia an identical missense mutation in the CBFA1/RUNX2 gene leading to a divergent craniofacial phenotype was determined. The results indicate marked variability in the phenotypical expression of CBFA1/RUNX2 mutations.