Correlation of abnormal rapid FISH and chromosome results from amniocytes for prenatal diagnosis

Rapid fluorescence in situ hybridization (FISH) performed on 1,788 amniocenteses, using Aneuvision (Vysis) probes for chromosomes 13, 18, 21, X, and Y, over several years, yielded 115 cases with percentages of aneuploidy between 4 and 100%. All cases above 60% were confirmed to be positive by chromosome analysis. Fifteen of forty-one cases that would be considered inconclusive by generally accepted criteria (i.e. with less than 60% of cells with an abnormal signal pattern) revealed lower cutoffs to be positive when confirmed by chromosome analysis. For trisomy 21, 6 cases with percentages from 36 to 57% were positive; 4 of 7 cases with percentages from 22.5 to 33% were positive; 11 cases with percentages of 13% or less were negative. Similar trends were found for aneuploidies of 13, 18, X, and Y. However, the number of abnormal cases is still too small to determine definitive cutoffs in the <60% gray zone. An average of 57 metaphases was analyzed for cases with FISH percentages below 60%. Despite the wide range of abnormal FISH percentages for chromosomally positive cases, we found no examples of autosomal mosaicism in this series. Although sex chromosome mosaicism was cytogenetically evident in several cases, there was little direct correlation between cytogenetic and rapid FISH results. FISH results involving sex chromosomes were more frequently confounded by maternal cell contamination and other technical factors.