International, collaborative assessment of 146 000 prenatal karyotypes: expected limitations if only chromosome-specific probes and fluorescent in-situ hybridization are used

Abstract

The development of chromosome-specific probes (CSP) and fluorescent in-situ hybridization (FISH) has allowed for very rapid identification of selected numerical abnormalities. We attempt here to determine, in principle, what percentage of abnormalities would be detectable if only CSP-FISH were performed without karyotype for prenatal diagnosis. A total of 146 128 consecutive karyotypes for prenatal diagnosis from eight centres in four countries for 5 years were compared with predicted detection if probes for chromosomes 13, 18, 21, X and Y were used, and assuming 100% detection efficiency. A total of 4163 abnormalities (2.85%) were found including 2889 (69. 4%) (trisomy 21, trisomy 18, trisomy 13, numerical sex chromosome abnormalities, and triploidies) which were considered detectable by FISH. Of these, 1274 were mosaics, translocations, deletions, inversions, rings, and markers which would not be considered detectable. CSP-FISH is a useful adjunct to karyotype for high risk situations, and may be appropriate in low risk screening, but should not be seen as a replacement for karyotype as too many structural chromosome abnormalities will be missed.

Evaluation of Microfluidics-FISH method in prenatal diagnosis

“…As available kit of FISH probes is focused on 13, 18, 21, X and Y chromosome aneuploidies, this abnormality could not be detected and presents limitation of methods based on FISH. Almost 30% of chromosomal aberrations might not be detected by FISH based methods in prenatal diagnosis, concluded Evans et al in their study which was an international, collaborative assessment of 146 000 prenatal cytogenetic results [10]. However, the question arises about their clinical relevance as balanced translocations were also counted.…”

Antenatal Detection of Trisomy 21 from Mosaic Translocation in Uncultured Amniocytes by Interphasic FISH

“…Indeed, in their series of six trisomies 21 examined, on 345 cell nuclei analyzed, there were 282 (87.7%) of nuclei with 3 signals with a percentage of false positive zero and 3 (5% and 5%) false negative. Evans et al [20] found that the interphasic FISH detects only 70% of cytogenetic abnormalities. Indeed, Thein et al [18], in their study, reported 14 cases not detected by interphasic FISH: which were deletion, translocation, insertion, mosaicism, and duplication.…”

“…For most authors [18][19][20], the interphasic FISH on uncultured amniocytes is a quick method for the detection of the most frequent aneuploidies (on chromosomes 21, 13, 18, X, 8). In addition, the quick confirmation of the results would reduce the mother anxiety.…”

Non-invasive prenatal testing (NIPT): limitations on the way to become diagnosis

“…Prenatal diagnosis of chromosome abnormalities is performed by conventional cytogenetic analysis using in vitro culture of fetal nucleated cells retrieved by amniocentesis, chorionic biopsy or fetal blood sampling. The need for rapid prenatal diagnosis led to the use of the FISH assay; however, the cost of this procedure has limited its application in specific cases [3]. The quantitative fluorescent PCR (QF-PCR) test allows prenatal diagnosis of major numerical abnormalities of chromosomes 21, 18, 13, X and Y in a few hours after sampling [15].…”

“…The 1997 discovery of free fetal DNA in maternal plasma launched scientists' efforts to establish a reliable method for non-invasive prenatal diagnosis [3]. Several recent studies have demonstrated that the most effective screening method for trisomy 21, with a detection rate of more than 99% and false-positive rate of about 0.1%, is derived from examination of cell-free DNA (cf DNA) in maternal plasma [4][5][6][7][8][9][10][11][12][13].…”