cfDNA deconvolution via NIPT of a pregnant woman after bone marrow transplant and donor egg IVF

Abstract

Cell-free DNA is known to be a mixture of DNA fragments originating from various tissue types and organs of the human body and can be utilized for several clinical applications and potentially more to be created. Non-invasive prenatal testing (NIPT), by high throughput sequencing of cell-free DNA (cfDNA), has been successfully applied in the clinical screening of fetal chromosomal aneuploidies, with more extended coverage under active research.In this study, via a quite unique and rare NIPT sample, who has undergone both bone marrow transplant and donor egg IVF, we investigated the sources of oddness observed in the NIPT result using a combination of molecular genetics and genomic methods and eventually had the case fully resolved. Along the process, we devised a clinically viable process to dissect the sample mixture.Eventually, we used the proposed scheme to evaluate the relatedness of individuals and the demultiplexed sample components following modified population genetics concepts, exemplifying a noninvasive prenatal paternity test prototype. For NIPT specific applicational concern, more thorough and detailed clinical information should therefore be collected prior to cfDNA-based screening procedure like NIPT and systematically reviewed when an abnormal report is obtained to improve genetic counseling and overall patient care.

Noninvasive prenatal screening in a pregnant woman with a history of stem cell transplant from a male donor: A case report and literature review

“…Our literature search yielded eight articles published between January 1, 2008 and January 1, 2023 (Balaguer et al., 2021 ; Balslev‐Harder et al., 2017 ; Bianchi et al., 2015 ; Byers et al., 2019 ; Neofytou et al., 2018 ; Neufeld‐Kaiser et al., 2015 ; Wilkins‐Haug et al., 2018 ; Zhu et al., 2021 ) that included details of eight women who had received transplants from male donors prior to undergoing NIPS. These data are shown in Table 2 .…”

“…Pregnant women who have undergone transplantation typically have three types of cfDNA in their plasma: fetal, maternal, and donor cfDNA. Zhu et al (2021) analyzed the cfDNA composition in a pregnant woman who had received a bone marrow transplant from a male donor and was carrying a male fetus. Using Y chromosomedependent and Y chromosome-independent methods, they found that the maternal plasma contained 72.64% donor cfDNA, 9.36% fetal cfDNA, and 18.00% maternal cfDNA.…”

“…These authors hypothesized that this discrepancy could be attributable to donor-derived Y chromosome cfDNA having been released into the maternal plasma. Additionally, the data from previous studies indicate that stem cell/bone marrow transplants from male donors have a greater impact on fetal fraction based on the presence of the Y chromosome than do organ transplants from male donors (Balaguer et al, 2021;Neofytou et al, 2018;Zhu et al, 2021). For example, Balaguer et al (2021) reported a pregnant woman who had received a bone marrow transplant in whom the fetal fraction based on the Y chromosome was 73.3%.…”

Combining Z-Score and Maternal Copy Number Variation Analysis Increases the Positive Rate and Accuracy in Non-Invasive Prenatal Testing

“…For this case, we also used CNV-seq on placental tissue to yield a results of 47,XY,+21, thus excluding CPM shown in Figure 2 . Another factor that can interfere with NIPT results is history of transplantation ( Zhu et al, 2021 ). In our study, a pregnant woman received a bone marrow transplant from a male donor 7 years ago.…”

The impact of preanalytical variables on the analysis of cell-free DNA from blood and urine samples

“…Fetal noninvasive prenatal testing (NIPT) based on cfDNA levels was the first successful application of cfDNA in health monitoring ( Schmid et al, 2018 ). Recent studies have explored the role of cfDNA in various areas, including NIPT ( Zhu et al, 2021 ), cancer ( Nabet et al, 2020 ), diabetes ( Humardani et al, 2023 ), cardiovascular diseases ( Polina et al, 2020 ), organ transplantation ( Wolf-Doty et al, 2021 ), autoimmune diseases ( Mondelo-Macia et al, 2021 ), and sepsis ( Lenz et al, 2022 ). However, the progress of most related studies remains in the preliminary stage, likely due to the challenges presented by preanalytical variables.…”