Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, China.
International Department, The Affiliated High School of SCNU, Guangzhou, 510630, China.
Arch Oral Biol. 2019 Jan;97:131-136. doi: 10.1016/j.archoralbio.2018.10.025. Epub 2018 Oct 23.
Tooth agenesis (TA) is featured by congenital loss of teeth, and can be divided into two subtypes, non-syndromic TA (NSTA) and syndromic TA (STA). Although 12 candidate genes of NSTA have been revealed, the genetic basis of NSTA needs to be further studied. We noticed an overlap of candidate genes between NSTA and STA, and hypothesized that some candidate genes of STA may be new candidate genes of NSTA.
Sanger sequencing, whole exome sequencing, bioinformatics analyses and immunohistochemical staining were performed to reveal the genetic basis of the patients in a family with NSTA.
No pathogenic mutation was found in the 12 candidate genes of NSTA. We screened the variants of 76 STA candidate genes and identified a novel pathogenic mutation c.G908C (p.R303 P) in Keratinocyte Differentiation Factor 1 (KDF1). This mutation was cosegregated with the disease in the family. Bioinformatics analyses predicted the mutation to be pathogenic. Immunohistochemical staining of kdf1 in developing tooth germs indicated that kdf1 expression is important for the development of teeth.
This study identified KDF1 as a novel candidate gene for NSTA. STA candidate genes may be a promising source of new NSTA genes.
牙齿先天缺失（TA）的特征是先天性牙齿缺失，可分为非综合征性 TA（NSTA）和综合征性 TA（STA）两种亚型。尽管已经揭示了 12 个 NSTA 的候选基因，但 NSTA 的遗传基础仍需要进一步研究。我们注意到 NSTA 和 STA 的候选基因之间存在重叠，因此假设 STA 的一些候选基因可能是 NSTA 的新候选基因。
对一个 NSTA 家系患者进行 Sanger 测序、全外显子组测序、生物信息学分析和免疫组织化学染色，以揭示其遗传基础。
在 12 个 NSTA 的候选基因中未发现致病性突变。我们筛选了 76 个 STA 候选基因的变异体，在角蛋白细胞分化因子 1（KDF1）中发现了一个新的致病突变 c.G908C（p.R303P）。该突变在家系中与疾病共分离。生物信息学分析预测该突变具有致病性。发育中牙胚的 kdf1 免疫组织化学染色表明，kdf1 的表达对牙齿的发育很重要。
本研究将 KDF1 鉴定为 NSTA 的一个新候选基因。STA 候选基因可能是 NSTA 新基因的有前途的来源。
