Open Journal of Stomatology, 2013, 3, 402-410 OJST http://dx.doi.org/10.4236/ojst.2013.38068 Published Online November 2013 (http://www.scirp.org/journal/ojst/ ) Cleidocranial dysplasia with a rare mutation: Study of a family with review of literature Ahmet Ercan Sekerci 2* , Burhan Balta 1 , Oğuzhan Bahadir 1 , Yildiray Sisman 2 , Munis Dundar 1 , Turgut Tursem Tokmak 3 , Stefan Mundlos 4 1 Department of Medical Genetics, Faculty of Medicine, Erciyes University, Kayseri, Turkey 2 Department of Oral Diagnosis and Radiology, Faculty of Dentistry, Erciyes University, Kayseri, Turkey 3 Department of Radiodiagnostics, Faculty of Medicine, Erciyes University, Kayseri, Turkey 4 Institute of Medical Genetics, Charité-Universitaetsmedizin, Berlin, Germany Email: * aercansekerci@hotmail.com Received 13 September 2013; revised 15 October 2013; accepted 23 October 2013 Copyright © 2013 Ahmet Ercan Sekerci et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Introduction: The present study was aimed at ad- vancing the understanding of the pathogenesis of cleidocranial dysplasia (CCD) by presenting a case study based on history, physical examination, typical radiological features, and molecular analysis and a review of the literature. Methods: This study began with a 23-year-old boy (proband) who was referred to the department of oral and maxillofacial radiol- ogy with chief complaint of the upper-left first molar tooth and routine dental examination. While evalu- ating the panoramic radiograph, the patient had ap- proximately 57 teeth in his both of the jaws. Clinical, radiographical and molecular features of the pro- band, two siblings and their parents were examined and then, DNA analysis was performed. Results: Overall, we present 3 CCD patients with a mutation in the VWRPY motif. The deletion of c. 1754_1757 delTTTG (NM_001024630.2) is determined and it leads to a frame shift mutation and stop codon, p. V585Gfs56X. Conclusions: The present study em- phasized the importance of further clinical and mo- lecular investigation when even a single case of CCD is identified within a family. This is the first study performed in Turkey about a family with a mutation in the VWRPY motif. Genotype-phenotype associa- tion studies in individuals with CCD are necessary to provide important insights into molecular mechanisms associated with this disease. Keywords: Cleidocranial Dysplasia; Mutation; RUNX2; Gene; Impacted Supernumeraries 1. INTRODUCTION Cleidocranial dysplasia (CCD), also known as Marie and Sainton disease [1] or cleidocranial dysostosis, is a rare congenital defect of autosomal dominance inheritance that is characterized by persistently open sutures or de- layed closure of sutures, hypoplasia or aplasia of the clavicles, cone-shaped thorax, short stature, supernumer- ary teeth, delayed eruption of permanent dentition and other skeletal anomalies [2]. Dental anomalies and some degrees of clavicular hy- poplasia seem to be consistent features of the disorder [3]. A variety of dental problems may occur in CCD. This condition is of clinical significance to dentistry due to the involvement of the facial bones, a prolonged retention of deciduous teeth and several impacted permanent succes- sors and supernumerary elements, sometimes accompa- nied by follicular cysts and eruptive pseudocysts [4]. CCD manifests itself as a condition in which teeth fail to erupt, which is thought to be due to the absence of cellu- lar cementum and an increase in the amount of acellular cementum of the roots of the affected teeth [5]. For these reasons, dental management is a significant aspect of the health care of affected persons [6]. This disorder is transmitted as an autosomal dominant trait or it’s caused by a spontaneous genetic mutation and is present at a frequency of one in one million individu- als [7]. It affects both males and females equally [8]. It has been demonstrated that mutation of the runt-related transcription factor 2 gene (RUNX2), located at chromo- some 6p21, is associated with CCD [9]. This gene en- codes a protein necessary for the correct functioning of osteoblastic differentiation and bone formation. RUNX2 has been shown to bind to the DNA sequence element called RUNX-binding site (PyGPyGGT) and to regulate * Corresponding author. OPEN ACCESS