Two years' prospective experience using fluorescence in situ hybridization on uncultured amniotic fluid cells for rapid prenatal diagnosis of common chromosomal aneuploidies.

A probe was generated from the YAC clone 831B9 that was suitable for the prenatal detection of trisomy 21 using fluorescence in situ hybridization (FISH). This probe was initially tested on a series of 650 unselected amniotic fluid samples prior to the karyotype being available. 630 were correctly identified as having two copies and 13 samples were correctly scored as having three copies of chromosome 21. Seven samples failed to produce a result. A trial was then initiated, reporting to clinicians the interphase FISH results before cytogenetic analysis had been performed. During the first 18 months of this trial 1504 samples were tested: 1467 were correctly identified as disomic and 35 samples were correctly scored as trisomic for chromosome 21. Two samples failed to produce a result. A chromosome 18 specific probe (LI.84) was employed where there was a relevant clinical indication (181 samples) and 10 samples were correctly scored as having three copies of chromosome 18. Thus, this approach appears to be reliable and is popular with both clinicians and patients due to the speed of the result. However, it does not replace chromosomal analysis on cultured cells, which detected a range of abnormalities besides the trisomies and triploidies detected by FISH.