Research Alert


SATB2-associated syndrome (SAS) is a multisystem disorder caused by mutation of human SATB2 gene. Tooth agenesis is one of the most common phenotypes observed in SAS. Our study aimed at identifying novel variant of SATB2 in a patient with SAS, and to investigate the cellular and molecular mechanism of tooth agenesis caused by SATB2 mutation.


We applied whole exome sequencing (WES) to identify the novel mutation of SATB2 in a Chinese patient with SAS. Construction and overexpression of wild-type and the mutant vector was performed, followed by functional analysis including flow cytometry assay, fluorescent immunocytochemistry, western blot, quantitative real-time PCR and Alizarin Red S staining to investigate its impact on hDPSCs and the underlying mechanisms.


As a result, we identified a novel frameshift mutation of SATB2 (c. 376_378delinsTT) in a patient with SAS exhibiting tooth agenesis. Human DPSCs transfected with mutant SATB2 showed decreased cell proliferation and odontogenic differentiation capacity compared with hDPSCs transfected with wild-type SATB2 plasmid. Mechanistically, mutant SATB2 failed to translocate into nucleus and distributed in the cytoplasm, failing to activate Wnt/β-catenin signaling pathway, whereas the wild-type SATB2 translocated into the nucleus and upregulated the expression of active β-catenin. When we used Wnt inhibitor XAV939 to treat hDPSCs transfected with wild-type SATB2 plasmid, the increased odontogenic differentiation capacity was attenuated. Furthermore, we found that SATB2 mutation resulted in the upregulation of DKK1 and histone demethylase JHDM1D to inhibit Wnt/β-catenin signaling pathway.


We identified a novel frameshift mutation of SATB2 (c.376_378delinsTT, p.Leu126SerfsX6) in a Chinese patient with SATB2-associated syndrome (SAS) exhibiting tooth agenesis. Mechanistically, SATB2 regulated osteo/odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway by regulating DKK1 and histone demethylase JHDM1D.

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