一例成骨不全Ⅱ型高危胎儿的产前基因诊断

Prenatal gene diagnosis of a high-risk fetus with osteogenesis imperfecta typeⅡ

目的对广东一疑似致死性侏儒症或成骨不全Ⅱ型的高危胎儿实施产前基因诊断,以阐明胎儿骨发育异常的真实病因,及时预防患胎出生。方法对经超声检查初诊为致死性侏儒症或成骨不全、已孕25周的高危胎儿,在抽取脐血制备DNA模板后,采用PCR-DNA直接测序法,分别对胎儿的FGFR3基因和COL1A1基因进行突变检测,然后对所发现的突变进行分析和鉴定。结果 FGFR3基因未发现病理性突变,而COL1A1基因发现一典型的杂合错义突变(c.3065G>T,p.G1022V),经查HGMD数据库证实为成骨不全Ⅱ型的致病性突变。结论 (1)此高危胎儿为成骨不全Ⅱ型患胎,应及时终止妊娠(胎儿已经引产,经复查证实与产前基因诊断结果完全一致)。(2)在超声初诊基础上,采用产前基因诊断可快速、有效对高危胎儿做出确诊,为出生缺陷的预防提供技术保障。

Objective To clarify the real pathogeny of the dysostoses of fetuses,the prenatal gene diagnosis of a Guangdong high-risk fetus suspected with osteogenesis imperfecta typeⅡor thanatophoric dwarfism was carried out,which stopped the birth of the suffering fetuses.MethodsThe high-risk fetus of 25 weeks was preliminarily diagnosed with thanatophoric dwarfism or osteogenesis imperfecta by ultrasonic test.The cord blood was extracted to make preparation for DNA template,PCR-DNA sequencing was used to detect the mutation of FGFR3 gene and COL1A1 gene,then the mutations were analyzed and identified.ResultsThere was no pathological mutation on the FGFR3 gene.There was a c.3065 G >T,p.G1022V heterozygosis missense mutation on the COL1A1 gene,which caused osteogenesis imperfecta typeⅡ;it was already reported on the HGMD.Conclusions(1) The high-risk fetus suffer with osteogenesis imperfecta-Ⅱ,which should be induced labour(the fetus had been induced labour already.The result of prenatal gene diagnosis was completely accordance with the result of rechecking).(2) On the basis of preliminary diagnosis of ultrasonic test,the high-risk fetuses can be quickly and effectively diagnosed by prenatal gene diagnosis,which provides the technical security for prevention of the birth defect.