Evaluation of the whole-genome non-invasive prenatal testing effectiveness for detection of rare chromosomal abnormalities based on the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O.Ott experience

Background. Non-invasive prenatal testing (NIPT) using whole-genome sequencing of DNA circulating in the pregnant woman blood is one of the most effective method for determining the risk of fetal chromosomal abnormalities without invasive interventions. This test, in addition to frequent abnormalities, allows to identify rare pathologies. However, the feasibility of whole-genome NIPT for detection of rare chromosomal abnormalities remains a subject of debate. Aim: to evaluate the effectiveness of whole-genome NIPT for the detection of rare fetus chromosomal abnormalities based on the D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology experience. Methods. In the period from December 2019 to May 2022, DNA samples isolated from the blood plasma of 4,600 women with singleton pregnancies were analyzed using whole genome sequencing technology. Results. In 182 (4.0%) cases, a high risk of fetal chromosomal abnormalities was found, of which 35 (19.2%) cases were rare pathologies. More common were trisomy on chromosome 16 (ten cases), on chromosome 19 (in three cases), less often - trisomy on chromosomes 8, 9, 20, 10, 22 (in two cases), on chromosomes 2, 3, 4, 5, 11, 12, 14, 15 (one case each), monosomy on chromosomes 21, 18 and 13 (one case each), one case of multiple aneuploidy. The invasive diagnostic results were obtained for 11 women, other patients refused invasive procedures. The identified rare anomalies were confirmed in 6 cases (54.5%).

chromosomal abnormalities, non-invasive prenatal testing, whole genome sequencing technology

1. Калашникова Е.А., Глотов А.С., Андреева Е.Н., Барков И.Ю., Бобровник Г.Ю., Дубровина Е.В., Жученко Л.А. Современное значение неинвазивного пренатального исследования внеклеточной ДНК плода в крови матери и перспективы его применения в системе массового скрининга беременных в Российской Федерации. Журнал акушерства и женских болезней. 2021;70(1):19-50. doi: https://doi.org/10.17816/JOWD56573

2. Козюлина П.Ю., Вашукова Е.С., Глотов А.С., Баранов В.С., Гладких Н.А. Способ неинвазивного пренатального скрининга анеуплоидий плода. Номер патента: RU 02712175 C1. Дата публикации: 24.01.2020.

3. Mardy A.H., Norton M.E. Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio? Prenat Diagn. 2021;41(10):1249-1254. doi: 10.1002/pd.6021.

4. Grati F.R., Bajaj K., Malvestiti F., Agrati C., Grimi B., Malvestiti B., Pompilii E., Maggi F., Gross S., Simoni G., Ferreira J. C. The type of feto-placental aneuploidy detected by cfDNA testing may influence the choice of confirmatory diagnostic procedure. Prenat Diagn. 2015;35(10):994-998. doi: 10.1002/pd.4659.

5. Grati F.R., Ferreira J., Benn P., Izzi C., Verdi F., Vercellotti E., Dalpiaz C., D’Ajello P., Filippi E., Volpe N., Malvestiti F., Maggi F., Simoni G., Frusca T., Cirelli G., Bracalente G., Re A. L., Surico D., Ghi T., Prefumo F. Outcomes in pregnancies with a confined placental mosaicism and implications for prenatal screening using cell-free DNA. Genet Med. 2020;22(2):309-316. doi: 10.1038/s41436-019-0630-y.

6. Carvalheira G., Oliveira M. M., Takeno S., Lima F. T., Meloni V. A., Melaragno M.I. 19q13.33→qter trisomy in a girl with intellectual impairment and seizures. Meta Gene. 2014 Oct 27;2:799-806. doi: 10.1016/j.mgene.2014.09.004.

7. Jung S.I., Cho H.S., Lee C.H., Kim K.D., Ha J.O., Kim M.K., Lee K.H., Hyun M.S. Two cases of trisomy 19 as a sole chromosomal abnormality in myeloid disorders. Korean J Lab Med. 2008 Jun;28(3):174-8. doi: 10.3343/kjlm.2008.28.3.174.