Abstract
RATIONALE: Supernumerary 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 CONCERNS: A family with the clinical diagnosis of supernumerary teeth, short stature and craniofacial dysplasia was examined. DIAGNOSES: Molecular 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. INTERVENTIONS: Whole 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. OUTCOMES: A 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. LESSONS: This 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.