A Novel Mutation of Gene CBFA1/RUNX2 in Cleidocranial Dysplasia

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterised by abnormal clavicles, patent sutures and fontanelles, supernumerary teeth, short stature, and a variety of other skeletal changes. The disease gene is CBFA1/RUNX2, which is mapped to chromosome 6p21. Inactivation of the CBFA1/RUNX2 gene by mutations is involved in the skeletal defects that occur in patients with CCD. CBFA1/RUNX2 controls the differentiation of precursor cells into osteoblasts and is essential for membranous as well as endochondral bone formation. In this study of a 14-yr-old boy with typical CCD phenotype, the authors found a novel CBFA1/RUNX2 gene mutation. All of the amplified segments from the patient's CBFA1/RUNX2 gene were identical to those obtained in controls, except for the one spanning the exon 7 and intron/exon boundary regions. Direct sequencing of the PCR product showed a heterozygous T-to-A transition mutation at nucleotide 1182 in exon 7, leading to Y394X mutation. The predicted protein product lacks 128 amino acids, including part of the PST domain. Identification of this novel mutation constitutes a further step in elucidating the pathogenesis of this autosomal disorder