A Novel Mutation of Gene CBFA1/RUNX2 in Cleidocranial ... - CiteSeerX

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KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos. S, Olsen BR, Selby PB, .... Emanuelli M, Pierella F,. Sartini D, Staibano S, Rubini C, De Rosa G. Genetic.
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Annals of Clinical & Laboratory Science, vol. 37, no. 2, 2007

A Novel Mutation of Gene CBFA1/RUNX2 in Cleidocranial Dysplasia

Lorenzo Lo Muzio,1 Stefano Tetè,2 Filiberto Mastrangelo,2 Angela Pia Cazzolla,3 Maria Grazia Lacaita,3 Maurizio Margaglione,4,5 and Giuseppina Campisi6 1Department of Surgical Sciences, University of Foggia, Foggia; 2Department of Oral Sciences, University of Chieti, Chieti; 3Department of Dentistry and Surgery, University of Bari, Bari; 4Department of Biomedical Sciences, University of Foggia, Foggia; 5IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo; and 6Department of Dental Sciences, University of Palermo, Palermo, Italy Abstract. 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. Keywords: cleidocranial dysplasia, CBFA1/RUNX2 gene, CBFA1/RUNX2 nonsense mutation Introduction Cleidocranial dysplasia (CCD), also known as cleidocranial dysostosis or Marie-Sainton disease, is characterized by defective development of the cranial bones, complete or partial absence of the clavicles, and other skeletal changes; CCD is often associated with immunodeficiency [1-7]. CCD is an autosomal dominant disorder of high penetrance, affecting skeletal ossification and tooth development. It has a prevalence of