Noninvasive prenatal screening for cystic fibrosis using circulating trophoblasts: Detection of the 50 most common disease‐causing variants

Abstract

Objectives: Cystic fibrosis (CF) is one of the most common severe autosomal recessive disorders. Prenatal or preconception CF screening is offered in some countries. A maternal blood sample in early pregnancy can provide circulating trophoblasts and offers a DNA source for genetic analysis of both the mother and the fetus. This study aimed to develop a cell-based noninvasive prenatal test (NIPT) to screen for the 50 most common CF variants.Methods: Blood samples were collected from 30 pregnancies undergoing invasive diagnostics and circulating trophoblasts were harvested in 27. Cystic fibrosis testing was conducted using two different methods: by fragment length analysis and by our newly developed NGS-based CF analysis.Results: In all 27 cases, cell-based NIPT provided a result using both methods in agreement with the invasive test result. Conclusion:This study shows that cell-based NIPT for CF screening provides a reliable result without the need for partner-and proband samples. Key points What's already known about this topic?� Many pregnant women are positive towards prenatal screening for Cystic fibrosis (CF).� The only current pregnancy marker is echogenic bowel in the second trimester, but this test has low sensitivity and specificity. What does this study add?� Prenatal screening for CF can be done using circulating trophoblasts isolated from maternal blood early in pregnancy � Circulating trophoblasts can provide screening for CF as a simple single-visit setup without the need for a paternal sample.The data will be included in a presentation by author Line Dahl Jeppesen at CoGEN in start of November 2022.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

How does cell‐based non‐invasive prenatal test (NIPT) perform against chorionic villus sampling and cell‐free NIPT in detecting trisomies and copy number variations? A clinical study from Denmark

“…Another strength of cbNIPT over cfNIPT is that the same blood sample used for aneuploidy and CNV detection can potentially be used for prenatal screening of monogenic disorders 13 . We have found that cbNIPT can also be used for screening for cystic fibrosis 13 and we are currently validating other monogenetic disorders in the same setup.…”

“…Thus, they constitute an attractive source for non-invasive prenatal testing for aneuploidies, sex chromosome aberrations (SCA), and pathogenic CNVs, [8][9][10][11][12] as well as monogenic disorders. 13 For example, whole genome amplification from 3 harvested fetal cells rendered enough DNA for both chromosomal microarray (CMA) and cystic fibrosis screening. 13 This provides a future opportunity for a wider screening using a blood sample only from the pregnant women without the need for partner samples.…”

“…However, once isolated, every cell comes with the potential of an entire fetal genome uncontaminated by maternal DNA. Thus, they constitute an attractive source for non‐invasive prenatal testing for aneuploidies, sex chromosome aberrations (SCA), and pathogenic CNVs, 8–12 as well as monogenic disorders 13 . For example, whole genome amplification from 3 harvested fetal cells rendered enough DNA for both chromosomal microarray (CMA) and cystic fibrosis screening 13 .…”

“…13 For example, whole genome amplification from 3 harvested fetal cells rendered enough DNA for both chromosomal microarray (CMA) and cystic fibrosis screening. 13 This provides a future opportunity for a wider screening using a blood sample only from the pregnant women without the need for partner samples.…”

Non-invasive prenatal diagnosis (NIPD): current and emerging technologies

“…Cell-free fetal nucleic acids are accompanied by a low number of fetal cells in the maternal bloodstream, namely trophoblastic cells derived from the placental tissue and early erythrocytes (i.e., red blood cells), which are also specific to the ongoing pregnancy [138,139] . These populations of cells can theoretically be isolated from peripheral maternal blood from as early as 6 weeks of pregnancy, although reportedly more reliably from 10-14 weeks, and offer a source of intact fetal chromosomal DNA for NIPD of monogenic conditions [140][141][142][143] . Obtaining a pure fetal cell population provides the benefit of having intact gDNA within which more complex pathogenic variants can be detected [144] , such as triplet repeat expansions [145] .…”