Rapid prenatal diagnosis of chromosome aneuploidies in 943 uncultured amniotic fluid samples by fluorescence in situ hybridization (FISH)

ABSTRACT

PURPOSE: Fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells offers the opportunity for rapid screening of aneuploidies and has become an integral part of the current practice in many clinical cytogenetics laboratories. Here, we retrospectively analyzed the results of interphase FISH in 943 amniotic fluid samples and assessed the efficiency of FISH for rapid detection of aneuploidies. METHODS: Interphase FISH for chromosome 13, 18, and 21 was performed in 943 consecutive amniotic fluid samples for rapid diagnosis of aneuploidies referred from 2004 to 2006. Karyotypes from standard cytogenetic analysis were compared to the FISH results. RESULTS: A total of 45 chromosomal rearrangements (4.8%) were found after conventional cytogenetic analysis of the 943 amniotic fluid. After exclusion of known familiar chromosomal rearrangements and inversions (2.1%, 20/943), 2.7% (25/943) were found to have chromosomal abnormalities. Of this group, 0.7% (6/943) were chromosomal abnormalities not detectable by FISH and 2.0% (19/943) were numerical abnormalities detectable by FISH. All 14 cases of Down syndrome (Classic type, 13 cases; Robertsonian type, 1 case) and 5 cases of trisomy 18 were diagnosed and detected by FISH and there were no false-positive or -negative results (specificity and sensitivity=100%). CONCLUSION: The present study demonstrates that FISH can provide a rapid and sensitive clinical method for prenatal identification of chromosome aneuploidies. However, careful genetic counseling is essential to explain the limitations of FISH, including the inability to detect all chromosomal abnormalities and the possibilities of uninformative or false-negative results in some cases.