Identification of a familial cleidocranial dysplasia with a novel RUNX2 mutation and establishment of patient-derived induced pluripotent stem cells

Abstract

Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disease associated with the gene RUNX2. Disease-specific induced pluripotent stem cells (iPSCs) have emerged as a useful resource to further study human hereditary diseases such as CCD. In this study, we identified a novel CCD-specific RUNX2 mutation and established iPSCs with this mutation. Biopsies were obtained from familial CCD patients and mutation analyses were performed through Sanger sequencing and next generation sequencing. CCD-specific human iPSCs (CCD-hiPSCs) were established and maintained under completely defined serum, feeder, and integration-free condition using a non-integrating replication-defective Sendai virus vector. We identified the novel mutation RUNX2_c.371C>G and successfully established CCD-hiPSCs. The CCD-hiPSCs inherited the same mutation, possessed pluripotency, and showed the ability to differentiate the three germ layers. We concluded that RUNX2_c.371C>G was likely pathogenic because our results, derived from next generation sequencing, are supported by actual clinical evidence, familial tracing, and genetic data. Thus, we concluded that hiPSCs with a novel CCD-specific RUNX2 mutation are viable as a resource for future studies on CCD.

Prevalence, clinical characteristics, and 3-dimensional radiographic analysis of supernumerary teeth in Guangzhou, China: a retrospective study

“…A single supernumerary tooth (68.2%) was the most common, followed by 2 ST (31.2%), 3 ST (0.3%) and 4 ST (0.2%). Multiple ST (≥ 5 ST) are very rare and are usually associated with a syndrome, such as cleidocranial dysplasia [ 6 ]. A similar study was reported by Bereket, and the results suggested that 77.4% of patients had one supernumerary tooth, 18.4% of patients had 2 ST, and 4.2% of patients had 3 or more ST [ 37 ].…”

“…Several scientific hypotheses have been put forward to explain the aetiology and development of ST including atavism, dichotomy of the tooth bud, hyperactivity of the dental lamina, and genetic factors [ 5 ]. It has been reported that genetics and heredity play a key role in the occurrence of ST, especially in patients with a syndrome or family history [ 6 ]. Environmental factors will increase individual genetic susceptibility [ 7 ].…”