一例新的WNT10A双等位基因复合杂合突变所致的单纯型多数牙先天缺失

›› 2019, Vol. 10 ›› Issue (4): 180-195.

一例新的WNT10A双等位基因复合杂合突变所致的单纯型多数牙先天缺失

郑静蕾,张刘陶,樊壮壮,吴君怡,余淼,刘洋,刘浩辰,韩冬

北京大学口腔医院修复科

收稿日期:2019-09-27 修回日期:2019-09-30 出版日期:2019-12-25 发布日期:2020-01-06
通讯作者: 韩冬 E-mail:donghan@bjmu.edu.cn
基金资助:
国家自然科学基金

A novel bi-allelic WNT10A compound heterozygous mutation in a patient with non-syndromic oligodontia

Received:2019-09-27 Revised:2019-09-30 Online:2019-12-25 Published:2020-01-06

摘要/Abstract

摘要： 目的：确定一例单纯型多数牙先天缺失家系的分子遗传学病因。方法：针对收集到的家系进行病史采集、临床检查、影像学检查、血样采集，提取患者DNA，进行全外显子组测序。将获得的测序结果与正常人类基因组比对，并进行Sanger测序验证。最后，利用人类外显子组整合数据库（Exome Aggregation Consortium，ExAC）、人类基因组整合数据库（Genome Aggregation Database，gnomeAD）、单核苷酸多态性数据库（The Single Nucleotide Polymorphism database，dbSNP）、耐受性分析（Sorting Intolerant from Tolerant，SIFT）、多态性表现型分析（polymorphism phenotyping，PolyPhen‐2）和突变筛选分析（Mutation Taster）等多种生物信息学数据库来筛选和确认导致该家系先天性缺牙的相关基因突变。结果：该家系中的先证者先天缺失恒牙22颗，为单纯型多数牙先天缺失，其父母和弟弟表型未见异常。全外显子测序结果显示先证者携带WNT10A双等位基因的复合杂合突变c.637A>G（p.G213S）和 c.985C>T（p.R329X）。进一步研究证实先证者的错义突变c.637A>G（p.G213S）遗传自父亲，而无义突变c.985C>T（p.R329X）遗传自母亲。先证者弟弟未携带任何突变。结论：本研究揭示了一例单纯型先天多数牙缺失的家系中致病的WNT10A的复合杂合错义突变及其遗传来源。该结果可用于遗传咨询和产前诊断，并有利于深入理解WNT10A突变在先天缺牙致病机制中的作用。

关键词: 单纯型先天缺牙, WNT10A, 复合杂合突变, 全外显子测序

Abstract: Objective: We collected a family with non-syndromic oligodontia, and tried to detect the genetic etiology. Methods: After the medical history, clinical examinations including imaging examination, and blood sample were collected, we isolated the genomic DNA and conducted the whole exome sequence (WES). All the results were aligned to the normal human genome, and verified by Sanger sequencing. A series of bioinformatics database such as Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomeAD), Single Nucleotide Polymorphism Database (dbSNP), Sorting Intolerant from Tolerant (SIFT), polymorphism phenotyping (PolyPhen-2), and Mutation Taster, were used for mutation screening and confirmation. Results: The proband of the family was congenital missing 22 permanent teeth, and his parents and little brother showed normal clinical manifestations. The consequences of WES indicated that the proband carried compound heterozygous WNT10A mutations [c.637A>G (p.G213S) and c.985C>T (p.R329X)]. Further studies confirmed that the proband's missense mutation c.637A>G(p.G213S) was inherited from his father, while the nonsense mutation c.985C>T (p.R329X) was inherited from his mother. The little brother did not carry any mutations. Conclusions: Our study revealed a novel WNT10A compound heterozygous mutation and its genetic origin in a family with non-syndromic oligodontia. This result can be used for genetic counseling and prenatal diagnosis, and will improve understanding the role of WNT10A mutations in the pathogenesis of congenital tooth agenesis.

郑静蕾张刘陶樊壮壮吴君怡余淼刘洋刘浩辰韩冬. 一例新的WNT10A双等位基因复合杂合突变所致的单纯型多数牙先天缺失[J]. , 2019, 10(4): 180-195.

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