Castaldo G, Martinelli P, Massa C, Fuccio A, Grosso M, Rippa E, Paladini D, Salvatore F
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli 'Federico II' and CEINGE scarl, Naples, Italy.
Clin Chim Acta. 2000 Aug;298(1-2):121-33. doi: 10.1016/s0009-8981(00)00284-9.
We performed prenatal diagnoses for cystic fibrosis in 32 high risk (1:4) couples (including a dizygotic pregnancy). Chorionic villi sampling did not cause abortion or fetal malformation in any case. The preliminary analysis of 9 short tandem repeats always excluded maternal contamination of the DNA extracted from chorionic villi and confirmed paternity. Twenty-two prenatal diagnoses were made by direct analysis of the mutations. In seven cases diagnosis was made by the analysis of intragenic polymorphisms; in three cases, we analyzed two extragenic polymorphisms. The prenatal diagnosis (including genetic counselling) was completed within 24 h from the sampling. Seven prenatal diagnoses revealed an affected fetus; all couples opted for therapeutic abortion. In 17 cases the fetus was heterozygote, and in seven cases it was non carrier of mutated alleles. In the twin pregnancy, mutations were DeltaF508/N1303K. Direct analysis of the DNA extracted from the two independent samples of chorionic villi revealed one fetus non carrier of mutated alleles and the other a carrier of the N1303K mutation. Analysis of the HPRT locus predicted both the fetuses as males. Furthermore, the genotype of each fetus was defined after birth. The prenatal diagnosis with chorionic villi sampling plays a key role in the prevention of cystic fibrosis. The laboratories must be equipped for both the direct analysis of mutations and for the analysis of a large number of polymorphisms. The preliminary analysis of short tandem repeats is recommended both to exclude maternal contamination and to confirm parentage.
我们对32对高风险(1:4)夫妇(包括1例双卵双胎妊娠)进行了囊性纤维化的产前诊断。在任何情况下,绒毛取样均未导致流产或胎儿畸形。对9个短串联重复序列的初步分析始终排除了从绒毛中提取的DNA的母体污染,并确认了亲子关系。22例产前诊断通过直接分析突变进行。7例通过分析基因内多态性进行诊断;3例分析了两个基因外多态性。产前诊断(包括遗传咨询)在取样后24小时内完成。7例产前诊断显示胎儿患病;所有夫妇均选择了治疗性流产。17例胎儿为杂合子,7例胎儿未携带突变等位基因。在双胎妊娠中,突变类型为DeltaF508/N1303K。对从两个独立的绒毛样本中提取的DNA进行直接分析,结果显示一个胎儿未携带突变等位基因,另一个胎儿携带N1303K突变。对HPRT基因座的分析预测两个胎儿均为男性。此外,每个胎儿出生后的基因型也得以确定。绒毛取样的产前诊断在预防囊性纤维化方面起着关键作用。实验室必须具备直接分析突变和分析大量多态性的能力。建议对短串联重复序列进行初步分析,以排除母体污染并确认亲子关系。