Development of cytogenomics for prenatal diagnosis: from chromosomes to single nucleotides: a review

Abstract

Prenatal diagnosis encompasses traditional cytogenetics and molecular-based techniques. In the new era of genomics, challenge to prenatal diagnosis has led to revised diagnostic strategies. In this review, we discuss the application of chromosomal microarray and a new prenatal diagnosis workflow in the public setting in Hong Kong. Using this prenatal diagnosis workflow, up to 40% of fetuses with structural anomalies can be identified with an underlying genetic aetiology, leaving the majority of cases undiagnosed. With the advancement of next generation sequencing, we are able to tackle the challenge of investigating chromosomal changes to single nucleotide variant level. Therefore, we also discuss whole exome sequencing, whole genome sequencing, and long-read sequencing, as well as their limitations and prenatal applications. This DNA-based technology should be evaluated for prenatal clinical application in Hong Kong.