Prenatal diagnosis of imprinted associated chromosome abnormalities identified by noninvasive prenatal testing (NIPT)

To explore the clinical value of noninvasive prenatal testing (NIPT) combined with chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV-seq), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), and fluorescence in situ hybridization (FISH) in the early screening of imprinted chromosome abnormalities. We retrospectively studied the prenatal diagnosis and pregnancy outcomes of 9 pregnant women with imprinted associated chromosome abnormalities via NIPT. All pregnant women received detailed genetic counselling and prenatal diagnosis. Karyotyping analysis, CNV-seq, CMA, FISH or MS-MLPA were performed on the amniotic fluid samples. We collected the intrauterine phenotypes via ultrasound and followed them up until the induction of labor or one year after birth. Six fetuses (6 out of 9) were diagnosed with regional abnormalities of Imprinting Disease. The most commonly diagnosed syndrome was 15q11-q13 duplication syndrome ( 3 out of 6), followed by mosaic trisomy 7 (2 out of 6) and Temple syndrome (1 out of 6). The other three fetuses (3 out of 9) were diagnosed with absence of heterozygosity (AOH). After genetic counselling, 4 pregnant women (4 out of 9) chose induced labor, 3 pregnant women (3 out of 9) chose spontaneous labor, and 2 pregnant women (2 out of 9) chose cesarean section. The widespread use of NIPT in prenatal screening provides more opportunities to detect rare chromosome aneuploidies (RCAs) and microdeletion/microduplication syndromes (MMSs) in mid-pregnancy. The combination of NIPT and other prenatal diagnostic technologies can help increase the possibility of detecting imprinting-related diseases with no phenotype or a late phenotype in utero.