华西口腔医学杂志2024，Vol.42Issue(5)：581-592,12.DOI:10.7518/hxkq.2024.2024090
非综合征型多数牙先天缺失家系中PAX9新突变的研究及PAX9突变导致非综合征型先天缺牙基因型—表型分析
A novel PAX9 variant in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants
摘要
Abstract
Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic 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 per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,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.Conclusion 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 mo-lars and the deciduous molars during the deciduous dentition.关键词
非综合征型先天缺牙/PAX9/全外显子组测序/基因型—表型Key words
non-syndromic tooth agenesis/PAX9/whole-exome sequencing/genotype-phenotype分类
医药卫生引用本文复制引用
靳占云,张红,杨玲,窦晨云,王晓雪,王金梅,沈文静,郭峻嘉,袁云云,孟令强,李慧,赵娅,任嘉宝,马永平,肖遵胜..非综合征型多数牙先天缺失家系中PAX9新突变的研究及PAX9突变导致非综合征型先天缺牙基因型—表型分析[J].华西口腔医学杂志,2024,42(5):581-592,12.基金项目
Special Project of Health Innovation of Hebei Provincial Department of Science and Technology(21377716D) （21377716D）
Natural Science Foundation of Hebei Province(H2022206246) （H2022206246）
2023 Hebei Provincial Gov-ernment Funded Clinical Medical Talents Training Proj-ect(ZF2023011) （ZF2023011）
Geriatric Disease Project of Hebei Provincial Department of Finance(361029) 河北省科技厅卫生健康创新专项(21377716D) （361029）
河北省自然科学基金精准医学项目(H2022206246) （H2022206246）
2023年政府资助临床医学优秀人才培养项目(ZF2023011) （ZF2023011）
河北省财政厅老年病项目(361029) （361029）
