Molecular karyotyping in the practice of prenatal diagnosis: experience, problems and prospects

Recently, there has been an active introduction of high-resolution diagnostic methods for detecting chromosomal abnormalities in humans. Thus, the use of microarray diagnostics allows detecting 6% more chromosomal abnormalities in fetuses with a normal karyotype based on the results of standard cytogenetic methods. At the same time, as part of the prenatal diagnosis, aCGH is used in much smaller amounts. This is primarily due to the receipt of a large amount of information and difficulties with its interpretation. This paper presents the results of using the aCGH method in prenatal diagnosis at the Research Institute of Medical Genetics of the Tomsk National Research Medical Center. In the framework of prenatal diagnosis, 44 samples of fetal material were examined using the aCGH method. Prenatal diagnosis using microarray in 20 cases (45%) allowed to identify chromosomal abnormalities, a balanced karyotype was detected in 21 samples (48%). In three cases (7%) the result was not obtained due to insufficient quantity or low quality of the biological material. Among the 20 cases with chromosomal abnormalities, 4 samples with aneuploidy and 16 samples with CNV. In 16 samples of fetal material without aneuploidy, 13 deletions and 10 duplications were identified. All the adjustments included in this list are not represented or represented by isolated cases in the Database of Genomic Variants. When analyzing the clinical significance of the CNV, were identified 11 pathogenic, 5 probably pathogenic and 5 CNV with uncertain significance. Pathogenic rearrangements were represented by 7 deletions and 4 duplications identified in 10 samples. In addition to the “Primary Finding” of pathogenic CNVs, so-called “Incidental Finding” of pathogenetically significant rearrangements are also detected. The identification of “Incidental Finding” is characteristic of all genome-wide studies and leads to the emergence of ethical issues related to informing patients and the possible termination of pregnancy. In the present study, five “Incidental Finding” pathogenic CNVs and five rearrangements with uncertain significance were identified. The results of this work indicate the need to use modern molecular cytogenetic methods for the prenatal diagnosis of chromosomal abnormalities. It is necessary to take into account the emergence of new methodological and ethical issues that are most acute when using these methods in prenatal diagnosis.