Long Reads, Short Time: Feasibility of Prenatal Sample Karyotyping by Nanopore Genome Sequencing.

To the Editor: Chromosomal abnormalities causing genomic imbalance are a major cause of congenital developmental defects and intellectual disability, constituting the leading cause of stillbirth and birth with malformations. In addition to the noninvasive prenatal test (1), considered a screening-level test, trisomy of chromosome 21, trisomy of chromosome 18, and trisomy of chromosome 13 are currently investigated by quantitative fluorescent PCR (2) and conventional karyotyping from fetal sample sources. Despite the advantage of significantly faster results compared with other methodologies, quantitative fluorescent PCR restricts the investigation to only those 3 chromosomes. Conversely, to obtain a conventional fetus karyotype, allowing detection of numerical abnormalities of all chromosomes, chorionic villus sampling (CVS)1 or amniotic fluid is routinely used as the source of a biological sample. Conventional karyotyping is usually performed after 10 days of ex vivo cell culture (although 2 days may suffice in case of higher cell recovery). The ability to detect fetal chromosomal aberrations is crucial, so that parents and the medical team can discuss different options; therefore, obtaining timely results represents a key variable for appropriate management, and available time is very limited in most instances. Herein, we demonstrate the …