To achieve a universal and comprehensive prenatal screening and diagnostic algorithms in Hong Kong, we explored the new territories and highlighted the novel trends in prenatal screening and diagnosis. Coming a long way from the pioneering work of CUHK on non-invasive prenatal testing (NIPT) toward a large-scale genome wide analysis by next generation sequencing. Non-invasive prenatal testing (NIPT) for common trisomies (21, 18, 13) has become a well-established, highly accurate screening tool in Down syndrome and other aneuploidy screening programs worldwide. NIPT by sequencing allows identification of sequence variants, being pathogenic or polymorphic, which in turn allowing for improved non-invasive prenatal screening. In this lecture, we are going to demonstrate value of concurrent SNP typing to improve the further success of NIPT to detect microdeletions and monogenic diseases. Although this represented a substantial advancement, the NIPT approach had important limitations as a screening test. Recognising this limitation, another methodological novelties developed in sequencing technologies, namely Low-pass genome sequencing (LP-GS) is developed at a reduced depth of coverage that supports affordable detection of genome-wide copy number variants (CNVs) and cryptic chromosome structural rearrangements. We validate LP-GS as a clinical diagnostic tool in cytogenetics and demonstrated it has the potential to revolutionize invasive prenatal testing by expanding the scope, accuracy, and affordability of detecting fetal genetic abnormalities beyond traditional methods like karyotyping and chromosomal microarray and even at a lower cost.
