Routine prenatal diagnosis of aneuploidy by FISH studies in high-risk pregnancies

Abstract

This study is a prospective clinical trial with fluorescent in situ hybridization (FISH) as a "routine" test for prenatal detection of the most common aneuploidies in high-risk pregnancies. Since April 1996, FISH studies with multicolor, commercially available, specific probes for chromosomes 13, 18, 21, X, and Y have been routinely performed in our cytogenetic laboratory on uncultured chorionic villous samplings (CVS), amniotic fluid samples, or fetal blood obtained by cordocentesis from patients with major or minor fetal anomalies detected by ultrasonography. Among the 4,193 prenatal samples analyzed between April 1996 and June 1998, routine FISH studies were ordered by the referring physicians on 301 (7.2%) cases. Aneuploidies were detected in 32 (10.6%) samples. Fourteen trisomy-21, 10 trisomy-18, 3 trisomy-13, 4 monosomies of X, and 1 case of triploidy were diagnosed by FISH. All 1,505 hybridizations were informative, and all 301 results were available and reported to the referring physicians in 24-48 hr. All relevant FISH results were confirmed by subsequent cytogenetic analysis. In 10 (3.8%) cases with normal FISH results, the final cytogenetic analysis revealed abnormal chromosomal rearrangements that could not be detected by the routine FISH studies. We conclude that rapid FISH analysis of interphase, uncultured fetal cells is an accurate and very sensitive method for routine prenatal diagnosis of the most common aneuploidies in high-risk pregnancies.

Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature

“…Although fluorescence in situ hybridization (FISH) can also be used as a rapid prenatal screen for common aneuploidies and for targeted analysis for known copy-number changes with higher resolution than cytogenetic analysis, it is labor intensive, requires prior knowledge of the region(s) of interest, and can only be used to screen one or a few genomic regions simultaneously. 24,25 CMA allows genome-wide detection of microscopic and submicroscopic chromosomal imbalances smaller than 100 kb. 7,17 For these reasons, CMA has become widely used in clinical diagnostics for postnatal and more recently, prenatal diagnosis.…”

Human molecular cytogenetics: Diagnosis, prognosis, and disease management

“…Furthermore, multiplex FISH has been used on sampled abortuses from spontaneous abortions for simultaneous detection of chromosomes 13,15,16,18,21,22, X, and Y. This advanced technique provides an unprecedented opportunity for screening of commonly occurring aneuploidies in a single experiment, thereby enabling rapid diagnosis and management [5,10,12].…”

Fetal liver hyperechogenicity on sonography may be a serendipitous sign of a transient myeloproliferating disorder

“…If this is the case, amniotic fluid and villi both offer a less risky alternative to fetal blood sampling. Introduction of new genetic tests has also been directed toward less invasive sampling, since the main advantage of fetal blood testing, for example, 'fast' karyotyping, can also be obtained by amniotic fluid and villi (Feldman et al, 2000;Mann et al, 2001). However, assay of biochemistry on fetal blood may be of value in cases of suspected infectious diseases, in order to allow the collection of additional data, which may help to understand the degree of compromise (Pratlong et al, 1994;Enders et al, 2001).…”