• Dan Ma, Xuxia Wang, Jun Guo, Jun Zhang, and Tao Cai.
• Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong, China Experimental Medicine Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, Shandong Beijing Key Laboratory for Genetics of Birth Defects, MOE Key Laboratory of Major Diseases in Children, Center for Medical Genetics, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Institute of Genomic Medicine, Wenzhou Medical University, Zhejiang, China.
• Medicine (Baltimore). 2018 Aug 1; 97 (32): e11328e11328.

RationaleSupernumerary teeth are those that teeth in excess number than the normal count. It is usually associated with genetic syndromes when present in more numbers. Several causal genes, such as APC, NHS, TRPS1, EVC and RUNX2, have been identified. However, etiology of supernumerary teeth remains largely unclear.Patient ConcernsA family with the clinical diagnosis of supernumerary teeth, short stature and craniofacial dysplasia was examined.DiagnosesMolecular genetic analysis found that mutation occurred in the RUNX2 gene. On the basis of this finding and clinical manifestations, the final diagnosis of cleidocranial dysplasia was made.InterventionsWhole exome sequencing (WES) of DNA samples was performed to identify the disease-causing mutation, including the affected child and mother as well as the healthy father.OutcomesA novel mutation of RUNX2 (c.473C>A; p.A158E) was identified in both patients, but not in normal family member and in-house database containing 3,000 Chinese Han individuals WES. This mutation was further confirmed by Sanger sequencing and predicted to be deleterious by several commonly used algorithms, including SIFT, PPT-2, MutationTaster and Proven. Furthermore, phenotype-genotype correlation analyses of all published 239 cases with different mutations in RUNX2 revealed significant association of supernumerary teeth and facial dysplasia with the Runt domain of the encoded protein.LessonsThis is the first WES study to identify genetic cause in Chinese patients with a novel RUNX2 mutation. Our findings expanded the mutation spectrum and clinical features of the disease and facilitated clinic diagnosis and genetic counseling.

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