选择性先天缺牙家系的表型与基因型分析：附2例报告

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。

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

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.