In silico size selection is effective in reducing false positive NIPS cases of monosomy X that are due to maternal mosaic monosomy X

• Published in: Prenatal diagnosis Vol. 37; no. 13; pp. 1305 - 1310
• Main Authors: Shubina, Jekaterina, Trofimov, Dmitry Yu, Barkov, Ilya Yu, Stupko, Olga K., Goltsov, Andrey Yu, Mukosey, Irina S., Tetruashvili, Nana K., Kim, Lyudmila V., Bakharev, Vladimir A., Karetnikova, Natalia A., Kochetkova, Taisya O., Krasheninnikova, Regina V., Bystritskiy, Andrey A., Sukhikh, Gennady T.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2017
• Subjects: Aneuploidy; Blood cells; Data analysis; Data processing; Deoxyribonucleic acid; DNA; DNA sequencing; Fetuses; Fluorescence; Fluorescence in situ hybridization; Genetic screening; Hybridization analysis; Monosomy; Population studies; Risk analysis
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.5178

Objectives The aim of this study was to establish maternal contribution to false positive noninvasive prenatal DNA screening (NIPS) results and develop the method to distinguish maternal and fetal origin of high‐risk monosomy X NIPS calls including mosaic maternal cases. Method A total of 906 women carrying singleton pregnancies have been recruited. Maternal plasma DNA semiconductor massive parallel sequencing was performed to detect common aneuploidies. For the case of high monosomy X risk call, analysis method to distinguish fetal and maternal monosomy X has been additionally applied. Results According to NIPS results, 18 patients had a high risk of fetal monosomy X. In 11 (61%) cases, fetal aneuploidy was confirmed by karyotyping. Other 7 cases were false positives. In 3 out of 7 cases, additional analysis based on in silico size selection was allowed to assume maternal monosomy X. In these cases, fluorescence in situ hybridization analysis confirmed mosaic monosomy X in maternal blood cells. Conclusion The prevalence of mosaic monosomy X karyotype is 0.3% (3/906)—10 times higher than published before. Additional in silico size‐selection and data analysis increases PPV for monosomy X from 61% to 73% for studied population.