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• A case of early-onset periodontitis with VitD deficiency and VitD receptor mutation was reported. • Vitamin D could promote early osteogenic differentiation of periodontal ligament stem cells (PDLSCs). • Vitamin D could inhibit TNF-α-induced inflammation of PDLSCs. Periodontitis is a chronic periodontal disease that contributes to tooth loss. In recent years, many animal studies have reported that vitamin D (VitD) deficiency results in chronic periodontitis. However, no studies have reported cases of early-onset periodontitis with VitD deficiency. This study reports a 5-year-old male patient with early-onset periodontitis, VitD deficiency and VitD receptor (VDR) mutation. The patient was treated with VitD and calcium, and received systematic periodontal treatment. During the 12-year treatment, the periodontal conditions of this patient were stable. Our in vitro study found that VitD could promote the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), bone gamma-carboxyglutamate protein (BGLAP), and VDR in the early osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Meanwhile, VitD could downregulate mRNA expression levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1β (IL-1β) and protein levels of IL-6 in the tumor necrosis factor-α (TNF-α) -induced inflammation of PDLSCs. Therefore, sufficient VitD supply can be a potential treatment for VitD deficiency induced early-onset periodontitis. [ABSTRACT FROM AUTHOR]