# Comprehensive Genetic Exploration of Fused Teeth by Whole Exome Sequencing
## 4 Discussion
_OBSCN_ is a gene encoding the obscurin protein, which is associated with myofibrlipogenesis and cytoskeletal arrangement [29]. Obscurin is mainly expressed in cardiac and skeletal muscle. Obscurin is associated with tumorigenesis and was reported to be observed more frequently in normal breast epithelium when compared to advanced-stage breast cancer biopsy samples [30,31]. Relationships between _OBSCN_ mutations and melanoma, glioblastoma, colorectal, lung, breast, and pancreatic cancer have been reported [32, 33, 34]. _OBSCN_ mutations are associated with numerous cancer types, including melanomas and pharyngeal and tongue origin basal cell carcinomas [35]. [PERSON] et al. [36] analysed human oral squamous cell carcinoma cells of pharyngeal and tongue origin, and identified seven _OBSCN_ mutations. _OBSCN_ is a complex gene, and its function is unclear. There are no reported associations between _OBSCN_ and tooth development or morphology. Further studies are needed to explore the association between _OBSCN_ and dentition. _SLC27A3_ variants were found in two of the seven patients with fused teeth, one from patient A-1 (c.1385G\(>\)A) and one from patient B-1 (c.1036C\(>\)T). _SLC27A3_ encodes fatty acid transport proteins (FATPs). Dysfunction of _SLC27A3_ may be associated with the aetiology of autism spectrum disorders. _SLC27A3_ was found in human neural stem cells, suggesting a relationship with the development of the central nervous system [37]. There are few reports on the function of the _SLC27A3_ gene. Hence, more research to investigate the function of the _SLC27A3_ gene is needed. _KIF25_ encodes a member of the kinesin-like protein family, which performs microtubule-dependent and ATP-dependent intracellular organelle transport and moves chromosomes during cell division [38]. Protein transport plays an essential role in cell formation and function. _KIF25_ activity has been observed in various cancer types [39] and is associated with chromatid segregation and cancer cell proliferation [40,41]. _KIF25_ was reported to be possibly associated with the incidence of Kawasaki disease [42]. The oral features of Kawasaki disease include redness, swelling, vertical cracking, bleeding of the lips, redness of the tongue, and hypertrophy of tongue papillae [43]. [PERSON] et al. [17] reported on the relationship between _KIF4A_ and taurodontism, microdontia, and dens invaginatus. _KIF4A_ encodes kinesin-related proteins and is similar in mechanism to _KIF25_. In this study, _KIF25_ was identified as a potential candidate for the aetiology of fused teeth, one of the morphological abnormalities of teeth. The two results indicate that kinesin family membersmay be related to tooth morphology. Further research is needed on the kinesin family members and tooth morphology. Three variants of _ERCC6_ (c.2204G\(>\)T) and _SLC27A3_ (c.1036C\(>\)T and c.1385G\(>\)A) were more frequent in East Asians. Fused teeth were reported to be more frequent in Asian populations [2], which may be related to the higher observed frequency of candidate variants. Although we did not find _FGF8_ variants in our study, [PERSON] et al. [44] examined _FGF8_ using the mouse model and found a unique type of fused supernumerary incisors of the dens invaginatus phenotype. _FGF8_ is expressed in dental epithelium and is associated with tooth development [45]; it may represent a similar mechanism in terms of tooth development. The relevance to human teeth should, however, be further investigated. This study was limited by its sample size; the number of candidate variants was vast, requiring further studies to narrow this discrepancy. In the next stage, WES analysis of larger families and verification of the phenotype-genotype correlations of candidate variants using knockout mice are required. In addition, because the incidence of fused teeth varies by race, studies in diverse ethnic groups may also provide compelling information. In this study, we successfully identified variants associated with the incidence of fused teeth.