Department of Periodontics, Shenzhen Stomatological Hospital, Southern Medical University, Shenzhen, China.
Biomol Biomed. 2024 Jan 3;24(1):73-81. doi: 10.17305/bb.2023.9282.
The aim of this study was to screen potential susceptibility genes using whole-exome sequencing (WES) in 15 Han Chinese patients with stage III or IV periodontitis and to evaluate the quantity and quality of genomic DNA extracted from saliva. DNA was extracted from saliva epithelial cells, quality-tested, and then subjected to WES and bioinformatics analyses. All variation loci were analyzed and interpreted following the American College of Medical Genetics and Genomics (ACMG) criteria. Candidate pathogenic variation loci were identified and verified using Sanger sequencing. Correlation and functional analyses of the candidate genes were used to identify potential susceptibility genes in patients with severe periodontitis. LFNG, LENG8, NPHS1, HFE, ILDR1, and DMXL2 genes were identified in over two cases each with shared mutations. Following these analyses, the DMXL2 gene was identified as being associated with stage III and IV periodontitis. These results suggest a potential pathophysiological risk mechanism for periodontitis, but need to be verified through larger clinical studies and mechanistic experiments to determine the pathogenicity of these gene mutations and their generalizability to a wider population of periodontitis patients. By screening candidate pathogenic variation loci using WES in 15 Han Chinese patients with stage III or IV periodontitis, our study could provide a pipeline and feasibility support for the identification of susceptibility genes in patients with stage III and IV periodontitis.
本研究旨在通过全外显子组测序（WES）筛选 15 例汉族 III 或 IV 期牙周炎患者的潜在易感基因，并评估从唾液中提取的基因组 DNA 的数量和质量。从唾液上皮细胞中提取 DNA，进行质量检测，然后进行 WES 和生物信息学分析。所有变异位点均按照美国医学遗传学与基因组学学院（ACMG）标准进行分析和解释。使用 Sanger 测序对候选致病性变异位点进行鉴定和验证。通过候选基因的相关性和功能分析，确定严重牙周炎患者的潜在易感基因。在两个或两个以上病例中发现 LFNG、LENG8、NPHS1、HFE、ILDR1 和 DMXL2 基因存在共享突变。经过这些分析，DMXL2 基因被确定与 III 期和 IV 期牙周炎有关。这些结果提示了牙周炎潜在的病理生理风险机制，但需要通过更大的临床研究和机制实验来验证这些基因突变的致病性及其在更广泛的牙周炎患者群体中的普遍性。通过对 15 例汉族 III 或 IV 期牙周炎患者进行 WES 筛选候选致病性变异位点，本研究可为鉴定 III 期和 IV 期牙周炎患者的易感基因提供一个可行的方法和可行性支持。
