Tommerup N, Søndergaard F, Hanauer A, Oberle I, Bang J, Barbi B, Bech B, Davies K, Froster-Iskenius U, Gustavson K H
John F. Kennedy Institute, Glostrup, Denmark.
Prenat Diagn. 1991 Aug;11(8):609-19. doi: 10.1002/pd.1970110818.
Early prenatal diagnosis of the fragile X was attempted in 44 pregnancies, including one twin pregnancy at risk of Martin-Bell (MB) syndrome. The sex ratio was 24M:21F. The fragile site was reproducibly demonstrated in cultured chorionic villus (CV) cells in eight male and five female fetuses. Six of the male and three of the female fetuses were terminated. Simultaneous RFLP analysis provided confirmative data with flanking DNA markers in 3 of 13 analysed cases. Recombination and/or non-informativeness at available distal and/or proximal loci were found in nine cases. In one male fetus, discordance between the haplotype and cytogenetics (fragile-X-negative) suggested the presence of a normal male transmitter, a double meiotic cross-over within the region, or a false-negative cytogenetic diagnosis. However, discordance between prenatal and post-termination/postnatal cytogenetic findings was not observed in this series. The use of excess thymidine for induction of the fragile X in cultured CV cells provided in the majority of cases a safe and rapid method for cytogenetic diagnosis, with options for early induced termination in fragile-X-positive pregnancies, for simultaneous RFLP analysis, and for subsequent second-trimester analysis of fetal blood in complicated cases.
对44例妊娠进行了脆性X综合征的早期产前诊断，其中包括1例有患马丁-贝尔（MB）综合征风险的双胎妊娠。性别比为24男:21女。在8例男性胎儿和5例女性胎儿的培养绒毛膜绒毛（CV）细胞中可重复性地显示出脆性位点。6例男性胎儿和3例女性胎儿被终止妊娠。在13例分析病例中的3例中，同时进行的限制性片段长度多态性（RFLP）分析提供了侧翼DNA标记的确认数据。在9例中发现了可用远端和/或近端位点的重组和/或信息不充分情况。在1例男性胎儿中，单倍型与细胞遗传学结果（脆性X阴性）之间的不一致表明存在正常男性传递者、该区域内的双减数分裂交叉，或细胞遗传学诊断假阴性。然而，在本系列中未观察到产前与终止妊娠后/产后细胞遗传学结果之间的不一致。在培养的CV细胞中使用过量胸苷诱导脆性X，在大多数情况下为细胞遗传学诊断提供了一种安全、快速的方法，为脆性X阳性妊娠早期诱导终止妊娠、同时进行RFLP分析以及对复杂病例进行孕中期胎儿血液后续分析提供了选择。
