两例遗传性凝血因子Ⅴ缺乏症的产前诊断

Prenatal diagnosis for two families of congenital factor V deficiency

目的根据2个凝血因子V（factorV，FV）缺乏症家系已确定的突变位点（G16088C和G69969T）进行遗传咨询并提供产前诊断。方法于12周胎龄采集绒毛膜并提取DNA，通过分析微卫星DNA鉴定绒毛膜DNA未被母体细胞污染。分别扩增12周胎龄绒毛膜、22周胎龄脐血和出生6个月后静脉血FV第3及23外显子片段并测序分析，并分别检测22周胎龄脐血及出生6个月后静脉血FV的活性。结果家系1胎儿携带G16088C杂合突变，脐血及外周静脉血FV活性分别为15％及53％；家系2胎儿未携带G69969T突变，为正常基因型，脐血及外周静脉血FV活性分别为32％及93％。出生后随访证实2个婴儿均生长发育正常，无出血倾向。结论胎儿基因型与表型一致，在国际上首次为2个遗传性FV缺乏症家系提供了产前诊断。

Objective To provide genetic consulting and prenatal diagnosis for two families with congenital factor V deficiency based on the known mutations of factor V gene （G16088C and G69969T）. Methods Chorionic DNA was obtained at 12 weeks of gestation and analyzed to exclude maternal cell contamination through microsatellite DNA analysis. It was then amplified with PCR and sequenced to determine the presence of mutations in exons 3 and 23. FV activity of the blood was assayed at 22 weeks of gestation and 6 months after birth. Results The fetus in case 1 was found to be a heterozygous carrier of the G16088C mutation, for whom FV activity of the cord blood and peripheral blood were 15 % and 53%, respectively. Fetus 2 did not carry the familiar G69969T mutation, for whom the FV activity of cord blood and peripheral blood has measured 32% and 93%, respectively. Follow-up studies demonstrated that the two infants were both in good health without a tendency for bleeding. Conclusion In both cases, the genotypes were consistent with the phenotypes. This is the first report of prenatal diagnosis of congenital F V deficiency.