一个非综合征型唇腭裂家系的致病基因鉴定

目的对一个非综合征型唇腭裂家系进行分子遗传学研究,探寻其致病原因。方法对该家系成员进行详细的体格检查和既往史调查,排除综合征型唇腭裂。对该家系1例患儿的基因组DNA进行全外显子组测序及生物信息学分析。筛查到候选致病基因突变位点后,采用Sanger测序对该家系成员及100名健康对照个体进行共分离分析和人群验证分析。结果全外显子组测序及疾病共分离分析显示,该家系患者IRF6基因第4外显子存在c.253A>G(p.Cys85Arg)变异,且该突变未在健康对照个体中检出,文献尚未见报道。结论IRF6基因第4外显子c.253A>G错义变异是导致该家系发病的原因。

Identification of pathogenic variant in a Chinese pedigree affected with non-syndromic cleft lip and palate

Objective To explore the genetic basis for a Chinese pedigree affected with non-syndromic cleft lip and cleft palate(NSCLP).Methods With informed consent obtained,members of the pedigree were subjected to clinical examination and history taking to exclude syndromic cleft lip and palate.One affected member was subjected to whole-exome sequencing and bioinformatics analysis.Candidate variant was verified by Sanger sequencing and co-segregation analysis of her family members and 100 unrelated healthy individuals.Results Whole-exome sequencing and co-segregation analysis showed that all affected members of this pedigree have carried a heterozygous missense c.253A>G(p.Cys85Arg)variant in exon 4 of the IRF6 gene,which has co-segregated with the phenotype and was not found among the 100 unrelated healthy individuals.Conclusion The missense c.253A>G variant in exon 4 of the IRF6 gene probably underlay the NSCLP in this pedigree.