RAPID PRENATAL-DIAGNOSIS OF CHROMOSOMAL ANEUPLOIDIES BY FLUORESCENCE INSITU HYBRIDIZATION - CLINICAL-EXPERIENCE WITH 4,500 SPECIMENS

Detection of chromosome aneuploidies in uncultured amniocytes is possi ble using fluorescence in situ hybridization (FISH). We herein describ e the results of the first clinical program which utilized FISH for th e rapid detection of chromosome aneuploidies in uncultured amniocytes. FISH was performed on physician request, as an adjunct to cytogenetic s in 4,500 patients. Region-specific DNA probes to chromosomes 13, 18, 21, X, and Y were used to determine ploidy by analysis of signal numb er in hybridized nuclei. A sample was considered to be euploid when al l autosomal probes generated two hybridization signals and when a norm al sex chromosome pattern was observed in greater than or equal to 80% of hybridized nuclei. A sample was considered to be aneuploid when gr eater than or equal to 70% of hybridized nuclei displayed the same abn ormal hybridization pattern for a specific probe. Of the attempted ana lyses, 90.2% met these criteria and were reported as informative to re ferring physicians within 2 d of receipt. Based on these reporting par ameters, the overall detection rate for aneuploidies was 73.3% (107/14 6), with an accuracy of informative results for aneuploidies of 93.9% (107/114). Compared to cytogenetics, the accuracy of all informative F ISH results, euploid and aneuploid, was 99.8%, and the specificity was 99.9%. In those pregnancies where fetal abnormalities had been observ ed by ultrasound, referring physicians requested FISH plus cytogenetic s at a significantly higher rate than they requested cytogenetics alon e. The current prenatal FISH protocol is not designed to detect all ch romosome abnormalities and should only be utilized as an adjunctive te st to cytogenetics. This experience demonstrates that FISH can provide a rapid and accurate clinical method for prenatal identification of c hromosome aneuploidies.