两个BDB1家系基因突变分析和产前诊断

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.2273CA(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.2273CA杂合突变,家系2中的Ⅲ4胎儿携带c.2273CA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.2273CA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。

Mutation analysis of two BDB1 pedigrees and prenatal diagnosis

Objective:To screen the mutation of related genes in patients with Brachy-dactyly 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 examina-tion 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. Sub-sequently,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 muta-tion 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 addi-tion,combining more than one index for prenatal diagnosis is recommended.