PRENATAL DIAGNOSIS OF CHROMOSOME PATHOLOGY ON INTERPHASE CELLS WITH FLUORESCENCE HYBRIDIZATION IN SITU — METHOD’S LIMITATION

Introduction. Molecular-cytogenetic and molecular methods are widely used in prenatal diagnosis for rapid detection of genomic mutations (trisomy 13, 18, 21). Aneuploidy screening is important for 35 year-old women. It is well known that the risk to born a child with chromosome pathology is higher among older mothers. The application of rapid aneuploidy testing by molecular and molecular-genetic methods as a stand-alone approach in prenatal diagnosis is greatly debated. The level of false-positive and false-negative results is 13.2–30%.

Objectives. To assess the clinical utility of molecular-cytogenetic methods as an express method in detecting chromosomal pathology in fetuses.

The aim of this study is to objectively evaluate FISH in prenatal diagnosis of chromosome pathology as stand-alone approach to women older than 35 years old.

Methods. Classical cytogenetic and molecular-cytogenetic methods (FISH) on metaphases and interphase cells.

Results and conclusions. We retrospectively reviewed the results of cytogenetic conventional investigation of 577 fetuses. CVS was performed specifically for advanced maternal age (35 years old). 30 abnormal karyotypes were found. Among them there were 21 fetuses with aneuploidy, 7 — with structural rearrengment and 2 fetuses — with marker chromosome.

Additional FISH investigation was used for 12 cases: in mosaic variants — 9 cases, to identify marker chromosome — 2 cases, to detect cryptic microdeletion — 1 case.

According to our results, FISH is highly informative test for identification of chromosomal mutation (marker chromosome, microdeletion, chromosomal rearrengements) and for identification of percent of mosaic clones.

However, it should be recognized that the rapid test for aneuploidy of chromosomes 13, 18, 21,  X and Y by FISH provides only a limited amount of information about the fetus’s karyotype. Retrospective analysis demonstrated that the fast FISH fails to detect 30 to 45% of the fetal chromosomal anomalies. The risk to receive false-negative results is near 48.4%, as our results demonstrate.