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In silico size selection is effective in reducing false positive NIPS cases of monosomy X that are due to maternal mosaic monosomy X
Author(s) -
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.
Publication year - 2017
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.5178
Subject(s) - monosomy , aneuploidy , biology , karyotype , genetics , obstetrics , medicine , chromosome , gene
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.