A novel noninvasive prenatal testing method for chromosomal rearrangements using maternal circulating cell‐free foetal DNA

Abstract

Dear Editor, At present, there is no noninvasive prenatal testing (NIPT) method available for pregnant women that one partner of couples carry balanced chromosomal rearrangements (BCRs). Here we present a novel NIPT method for detecting foetal chromosomal rearrangements based on haplotype analysis of maternal cell-free foetal DNA (cffDNA) and demonstrate its effectiveness and potential for clinical application in a cohort of 46 patients.BCRs are estimated to occur in approximately 0.5% of newborn infants 1 and the prevalence is even up to 4%-5% in individuals with fertility problems. 2 BCRs can result in infertility, recurrent miscarriages, or offspring with congenital malformations. 3,4 In general, invasive prenatal diagnosis (IPD) such as amniocentesis is recommended after pregnancy for couples in which one partner carries BCRs. However, IPD poses a 0.5% risk of miscarriage, infection and preterm labour. 5 Therefore, many couples decline IPD despite being BCR carriers. During pregnancy, maternal plasma contains a small percentage of cffDNA, which is an easily accessible source for the noninvasive determination of foetal chromosomal anomalies. The discovery has presented the possibility of noninvasive testing for genetic diseases; NIPT is now being increasingly used for detecting foetal chromosomal aneuploidies and monogenic disorders. 6,7 However, NIPT for structural chromosomal rearrangements (NIPT-SR) has not been available until now, despite its relatively high incidence.Core family-based haplotype linkage analysis has long been used to indirectly diagnose monogenic diseases, such as in preimplantation genetic testing (PGT) and NIPT. 7,8 In recent years, our team has illustrated haplotype analysis can also accurately detect balanced and unbalanced chromosome structural rearrangements in human embryos through PGT. 9 The concept that foetal karyotypes can be predicted by inherited parental haplotypes was first introduced for NIPT in this study. The general workflow of ourThis 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.