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浙江大学学报（医学版）
浙江大学学报（医学版）  2019, Vol. 48 Issue (4): 378-383    DOI: 10.3785/j.issn.1008-9292.2019.08.05
专题报道     
Van der Woude综合征一家系遗传学分析
许雨晴(),钱叶青,姚维妙,董旻岳*()
浙江大学医学院附属妇产科医院生殖遗传科 生殖遗传教育部重点实验室, 浙江 杭州 310006
Genetic analysis of a family of Van der Woude syndrome
XU Yuqing(),QIAN Yeqing,YAO Weimiao,DONG Minyue*()
Key Laboratory of Reproductive Genetics, Ministry of Education, Department of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
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摘要：

目的: 分析Van der Woude综合征一家系的临床和遗传学特征。方法: 采集先证者的脐带血和父母的外周血行全外显子组测序，初步确定候选致病基因。收集该家系9位成员的外周血进行Sanger测序验证、生物信息学分析、基因型与表型的相关性分析。结果: 先证者经超声诊断为唇腭裂，其父亲和祖母有下唇凹陷，其他成员无类似表型。先证者及其父亲、祖母IRF6基因第4号外显子均存在c.263A>G（P.N88S）错义突变，其他无表型的家系成员不存在该突变。结论: IRF6：c.263A>G（p.N88S）错义突变为该家系的致病原因，该突变在中国Van der Woude综合征家系中首次发现。
关键词： 唇裂/遗传学;  染色体障碍/遗传学;  腭裂/遗传学;  外显子;  干扰素调节因子类;  基因;  突变;  系谱    
Abstract:

Objective: To analyze clinical and genetic features of a family affected with Van der Woude syndrome. Methods: The umbilical cord blood of the proband and the peripheral blood of the parents were used for the whole exon sequencing to find the candidate gene.Peripheral blood of 9 members of the family were collected for Sanger sequencing verification, bioinformatics analysis and genotype-phenotype correlation analysis. Results: The proband was diagnosed with cleft lip and palate by ultrasound. His father and grandmother had hollow lower lip and all other family members did not have the similar phenotype. A missense c.263A>G (p.N88S) mutation was found in exon 4 of IRF6 gene in the proband, his father and his grandmother.The mutation was not found in other family members. Conclusion: A missense c.263A>G (p.N88S) mutation in IRF6 gene probably underlies the pathogenesis of Van der Woude syndrome in the family and the mutation has been firstly discovered in China.
Key words: Cleft lip/genetics    Chromosome disorders/genetics    Cleft palate/genetics    Exons    Interferon regulatory factors    Genes    Mutation    Pedigree
收稿日期: 2019-03-28 出版日期: 2019-10-30
:  R349.3  
基金资助: 浙江省重点研发计划(2019C03025)
通讯作者: 董旻岳     E-mail: 21718422@zju.edu.cn;dongmy@zju.edu.cn
作者简介: 许雨晴(1995—), 女, 硕士研究生, 主要从事妇产科学、生殖遗传学研究; E-mail: 21718422@zju.edu.cn; https://orcid.org/0000-0001-7591-3048
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引用本文:

许雨晴,钱叶青,姚维妙,董旻岳. Van der Woude综合征一家系遗传学分析[J]. 浙江大学学报（医学版）, 2019, 48(4): 378-383.

XU Yuqing,QIAN Yeqing,YAO Weimiao,DONG Minyue. Genetic analysis of a family of Van der Woude syndrome. J Zhejiang Univ (Med Sci), 2019, 48(4): 378-383.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.08.05    或    http://www.zjujournals.com/med/CN/Y2019/V48/I4/378

图 1  先证者(胎儿)超声图
图 2  先证者父亲、先证者祖母口腔及嘴唇照片
图 3  Van der Woude综合征患者的家系图
图 4  本家系 IRF6 基因突变位点示意图
图 5  本家系 IRF6 基因c.263位点Sanger测序结果
图 6  IRF6 基因c.263突变位点保守性分析
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