Dept. of Prosthodontics, School and Hospital of Stomatology, Hebei Medical University, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, Shijiazhuang 050017, China.
Dept. of Stomatology,the No.2 Hospital of Baoding, Baoding 071051, China.
Hua Xi Kou Qiang Yi Xue Za Zhi. 2024 Oct 1;42(5):581-592. doi: 10.7518/hxkq.2024.2024090.
This study aimed to identifyPAX9variants in non-syndromic tooth agenesis families of China, as well as to analyze the genotype⁃phenotype of non-syndromic tooth agenesis caused by PAX9variants, which can provide a basis for the genetic diagnosis of tooth agenesis.
We collected the data of 44 patients with non-syndromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023. Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members, and the variants were verified by Sanger sequencing. Pathogenicity analysis and function prediction of the variants were performed using bioinformatics tools. The correlation between the genotype of PAX9 variant and its corresponding phenotype was examined by reviewing 55 publications retrieved from PubMed. The studies involved 232 tooth agenesis patients with PAX9 variants.
A novel PAX9 c.447delG (p.Pro150Argfs62) and a reported PAX9 c.406C>T (p.Gln136) were identified in two Chinese families. Through bioinformatics analysis and three-dimensional structural modeling, we postulated that the frameshift variant was pathogenic. The outcome was the premature cessation of PAX9 protein, which caused severe structural and functional deficiencies. Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.
We identified the novel PAX9 c.447delG (p.Pro150Argfs*62) in a Chinese family of non-syndromic oligodontia, expanding the known variant spectrum of PAX9. The most susceptible tooth position for PAX9 variants of tooth agenesis was the second molars and the deciduous molars during the deciduous dentition.
本研究旨在鉴定中国非综合征性牙齿缺失家系中的 PAX9 变异，并分析 PAX9 变异引起的非综合征性牙齿缺失的表型-基因型相关性，为牙齿缺失的遗传诊断提供依据。
收集 2018 年至 2023 年在河北医科大学口腔医院就诊的 44 例非综合征性个别牙缺失患者的临床资料。对先证者及其核心家系成员的外周血进行全外显子测序，并通过 Sanger 测序验证变异。使用生物信息学工具对变异进行致病性分析和功能预测。通过检索 PubMed 数据库中 55 篇文献中报道的 232 例 PAX9 变异的牙齿缺失患者，分析 PAX9 变异的基因型与其相应表型的相关性。
在两个中国家系中发现了一个新的 PAX9 c.447delG (p.Pro150Argfs62) 和一个报道的 PAX9 c.406C>T (p.Gln136)。通过生物信息学分析和三维结构建模，我们推测移码变异是致病性的。结果是 PAX9 蛋白的提前终止，导致严重的结构和功能缺陷。总结 PAX9 基因型-表型关系发现，携带 PAX9 变异的患者常导致第二磨牙缺失。
我们在中国一个非综合征性个别牙缺失家系中发现了新的 PAX9 c.447delG (p.Pro150Argfs*62)，扩展了 PAX9 已知的变异谱。PAX9 变异引起的牙齿缺失最易感的牙齿位置是第二磨牙和乳牙列中的乳磨牙。
