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J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (4): 378-383    DOI: 10.3785/j.issn.1008-9292.2019.08.05
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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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 wordsCleft lip/genetics      Chromosome disorders/genetics      Cleft palate/genetics      Exons      Interferon regulatory factors      Genes      Mutation      Pedigree     
Received: 28 March 2019      Published: 30 October 2019
CLC:  R349.3  
Corresponding Authors: DONG Minyue     E-mail:;
Cite this article:

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.

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Van der Woude综合征一家系遗传学分析

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 
Fig 1 Ultrasound anomalies of the proband(fetus)
Fig 2 Mouths and lips of the father and grandmother of proband
Fig 3 Pedigree of a patient with Van der Woude syndrome
Fig 4 IRF6 gene mutation site
Fig 5 Sanger sequencing of IRF6 : c.263
Fig 6 Conservative analysis of IRF6 : c.263
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