两个BDB1家系基因突变分析和产前诊断

Mutation analysis of two BDB1 pedigrees and prenatal diagnosis

目的:对两个B1型短指(趾)(BDB1)家系进行基因突变分析和产前诊断。方法:提取两家系成员的外周血基因组DNA,应用PCR产物直接测序法对致病基因ROR2的第8外显子和一部分第9外显子进行突变筛查。提取两例孕妇血浆胎儿游离DNA和羊水细胞DNA,对胎儿进行产前诊断,超声检查评估胎儿表型。结果:两家系中发现同一杂合截短突变c.2273C>A(p.S758X)。无创产前筛查的结果表明,家系1中的Ⅲ3胎儿不携带c.2273C>A杂合突变,家系2中的Ⅲ4胎儿携带c.2273C>A杂合突变,该结果与羊水细胞DNA检测、超声检查的结果一致。结论:c.2273C>A杂合突变为两个BDB1家系的致病原因,推荐综合使用多个指标进行产前诊断。

Objective： To screen the mutation of related genes in patients with Brachydactyly type B1（BDB1） from two pedigrees and perform prenatal diagnosis for two affected pregnancies.Methods： DNA samples were extracted from peripheral blood of two pedigrees.Mutations were screened on the 8 and 9 exons of ROR2 using PCR direct sequencing.Cell-free fetal DNA was extracted from plasma of two pregnancies for noninvasive prenatal screening and genomic DNA was isolated from amniotic fluid cells for prenatal diagnosis.Ultrasound examination was carried out to observe the fetus ＇ phenotype. Results： Here we identified an identical nonsense mutation（c. 2273C 〉A,p.S758X） of ROR2 in affected patients of two families. Subsequently,noninvasive prenatal screening on two affected pregnant women using cell-free fetal DNA was performed and the results suggested that one fetus from pedigree 2 carried the mutation and the other from pedigree 1 did not. It was proved by prenatal diagnosis using amniotic fluid cells test and ultrasound examination. Conclusion： Our finding further confirmed that the heterozygous mutation c.2273C〉A was the causative defect in two BDB1 pedigrees.In addition,combining more than one index for prenatal diagnosis is recommended.