Van der Woude综合征一家系遗传学分析

Genetic analysis of a family of Van der Woude syndrome

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。

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.