Massive parallel sequencing-based non-invasive prenatal test (NIPT) identifies aberrations on chromosome 13

Abstract

Objective: We report data of non-invasive prenatal testing (NIPT) at Uppsala University Hospital between 2017-2022. Furthermore, we illustrate the potential capacity of massive parallel sequencing-based NIPT beyond identification of common trisomies.

Methods: Maternal blood samples were analyzed using the Verifi NIPT or VeriSeq NIPT assays. Diagnostic testing, performed on amniotic fluid samples, included QF-PCR, microarray (SNP-array) and metaphase FISH.

Results: Among 4532 NIPT tests performed between 2017-2022, 125 samples (2.76%) showed increased risk for trisomies 13, 18, 21 and sex chromosome aneuploidy. For three patients with normal NIPT result further microarray indicated other types of chromosomal rearrangement which were not analyzed by NIPT. For another patient (case 1) the Verifi NIPT indicated trisomy 13. Fetal fraction (FF) was estimated to be 10%. Confirmatory microarray detected a segmental duplication on chromosome 13, as well as a terminal duplication and a terminal deletion on chromosome 10. A complex karyotype was observed in the fetus with metaphase FISH. In the second case the VeriSeq NIPT indicated trisomy 13. FF was estimated to be 11%. Confirmatory microarray detected a mosaicism of trisomy 13 in 30 % of cells.

Conclusion: This study illustrates detection of peculiar abnormalities of chromosome 13 and supports potential to screen copy number variations with genome-wide NIPT.

Keywords: Complex karyotype; Massive parallel sequencing; Mosaicism; Non-invasive prenatal testing; Partial trisomy.