选择性先天缺牙家系的表型与基因型分析：附2例报告

doi:10.19438/j.cjoms.2022.03.017

中国口腔颌面外科杂志 ›› 2022, Vol. 20 ›› Issue (3): 298-302.doi: 10.19438/j.cjoms.2022.03.017

选择性先天缺牙家系的表型与基因型分析：附2例报告

蒋彩玲^1,2, 喻康², 吴轶群²

1.山西医科大学口腔医学院,山西太原 030001;
2.上海交通大学医学院附属第九人民医院口腔第二门诊部,上海交通大学口腔医学院, 国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海 200125

收稿日期:2021-11-11 修回日期:2021-12-29 出版日期:2022-05-20 发布日期:2022-05-20
通讯作者: 吴轶群,E-mail：wuyq1243@sh9hospital
作者简介:蒋彩玲（1995-）,女,硕士研究生,E-mail:JiangCL0627@163.com
基金资助:
上海市自然科学基金（21ZR1437700）; 上海交通大学医学院附属第九人民医院生物样本库专项基金（YBKB202101）

An analysis of phenotype, genotype in selected tooth agenesis: report of two cases

JIANG Cai-ling^1,2, YU Kang², WU Yi-qun²

1. School of Stomatology, Affiliated to Shanxi Medical University. Taiyuan 030001, Shanxi Province;
2. The Second Department of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology. Shanghai 200125, China

Received:2021-11-11 Revised:2021-12-29 Online:2022-05-20 Published:2022-05-20

摘要/Abstract

摘要： 目的: 探讨选择性先天缺牙患者的遗传学病因。方法: 对2例非综合征型先天缺牙患者进行临床检查、家系调查、影像学检查以及外周血采集,通过全外显子测序后与正常人类基因组比对,并进行Sanger测序验证,确定致病基因及突变位点后,进行蛋白结构预测和多物种保守性分析。结果: 2例选择性先天缺牙家系中家系1为散发型,家系2为家族型。全外显子测序结果显示,先证者1和先证者2分别存在LRP6无义突变（II:1, c.C1573T,p.R525X）以及移码突变（II-1, c.4611delT ,p.C1537fs）。蛋白结构分析表明,p.R525X使LRP6蛋白截短,为失功能突变。多物种保守性分析揭示位点在进化过程中高度保守,提示突变具备有害性。结论: 2例选择性先天缺牙家系可能由于LRP6突变导致,为遗传咨询和产前诊断提供了参考。

Abstract: PURPOSE: To explore the pathology of selective tooth agenesis. METHODS: The clinical manifestations of 2 patients were collected based on complete oral examinations, panoramic radiographs and pedigree information. Peripheral venous blood was taken from probands and their patients and DNA were extracted. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants. Aligned multi sequencing was conducted to predict the structure of LRP6 and LRP6 mutation. RESULTS: We discovered two probands with sporadic or heredity diagnosed selective tooth agenesis, proband 1 had a nonsense mutation (c.C1573T, p.R525X) of LRP6 and proband 2 had a frameshift mutation (c.4611delT, p.C1537fs) of LRP6. The predicting structure of LRP6 and LRP6 mutation illustrated that the mutation altered protein structure and created a premature stop codon. Aligned multi sequencing showed the LRP6 protein sequence highly conservative, suggesting that the mutation was hazardous. CONCLUSIONS: The results revealed two novel mutations of LRP6 of selective tooth agenesis which is helpful in prenatal diagnosis and genetic counseling.

Key words: Low-density lipoprotein receptor-related protein 6, Nonsense mutation, Frameshift mutation, Selected tooth agenesis

中图分类号:

R739.8

蒋彩玲, 喻康, 吴轶群. 选择性先天缺牙家系的表型与基因型分析：附2例报告[J]. 中国口腔颌面外科杂志, 2022, 20(3): 298-302.

JIANG Cai-ling, YU Kang, WU Yi-qun. An analysis of phenotype, genotype in selected tooth agenesis: report of two cases[J]. China J Oral Maxillofac Surg, 2022, 20(3): 298-302.

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选择性先天缺牙家系的表型与基因型分析：附2例报告

An analysis of phenotype, genotype in selected tooth agenesis: report of two cases

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