Cytogenetic analysis in the era of high-resolution molecular-cytogenetic methods: the potential of «reverse» karyotyping
Background: The introduction of high-resolution molecular-cytogenetic methods to clinical practice has allowed to reveal complex “cryptic” structural chromosomal rearrangements, which could not be detected by a standard cytogenetic analysis. The rearrangements larger than 5 Mb may be discovered by a repeated, or “reverse” karyotyping, performed after molecular studies. In these cases the target approach to investigation of a rearranged chromosome on metaphase spreads with the resolution of 500-800 bands should be used. The “reverse” karyotyping is necessary for further analyses of the diseased child’s family in order to find possible balanced rearrangements, as they cannot be revealed by molecular methods. The aim of the study: We performed additional cytogenetic analysis (“reverse” karyotyping) for 9 children with developmental and motor delay, congenital malformations and dysmorphic features, carrying unbalanced structural chromosomal abnormalities, detected by molecular karyotyping, as well as standard karyotyping and FISH for their parents. We used conventional cytogenetic methods, FISH, and molecular karyotyping with bioinformatic algorithms. Materials and methods: A repeated cytogenetic study (“reverse” karyotyping) was conducted for 9 children with developmental and motor delay, congenital malformations and dysmorphic features, carrying unbalanced structural chromosomal abnormalities, detected by molecular karyotyping, as well as standard karyotyping and FISH for their parents. We used conventional cytogenetic methods, FISH, and molecular karyotyping with bioinformatic algorithms. Results: The study provides cytogenetic, molecular-cytogenetic and clinical data on 9 children with developmental delay, congenital malformations and/or dysmorphisms, which carry unbalanced structural chromosomal abnormalities from 4.7 Mb in size, and data of their parents analyses. All 9 cases of “cryptic” chromosomal rearrangements were detected by a repetitive “reverse” karyotyping. In most cases the rearrangement represented a change of differential staining (banding) of the rearranged locus with no visible changes of the chromosome length. The parents’ analyses allow for correct genetic family counseling. Conclusion: The application of “reverse” karyotyping appeared to be effective in detection of small but cytogenetically visible rearrangements. Combined molecular-cytogenetic and cytogenetic methods should be used to obtain the most precise results in these families, including the diseased child.
Kolotii AD, Vorsanova SG, Yurov YuB, et al. Cytogenetic analysis in the era of high-resolution molecular-cytogenetic methods: the potential of «reverse» karyotyping. Research Results in Biomedicine. 2019;5(4):44-64. (In Russian)
DOI:10.18413/2658-6533-2019-5-4-0-4
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The study was partially carried out as part of state assignment No. AAAA-A18-118051590122-7, “Personified genomics of undifferentiated forms of mental retardation in children”, 2018-2020