Advances in Non-Invasive Diagnosis of Single-Gene Disorders and Fetal Exome Sequencing

Abstract

The main focus of genetic testing for prenatal diagnosis has mostly been the detection of fetal aneuploidy and subchromosomal abnormalities. However, with the advent of next-generation sequencing and the expanding knowledge on the contribution of single nucleotide variants to disease, the demand for monogenic disorder testing has increased considerably. Prenatal gene panel and exome sequencing on amniotic fluid samples have revealed that de novo and inherited pathogenic variants in single genes are an important cause of congenital anomalies. Furthermore, preconception and prenatal expanded carrier screening identify more carrier parents at risk of having children with recessive monogenic disorders, increasing the need for prenatal diagnostic testing for these disorders. This chapter provides an overview of testing approaches for single-gene disorders in non-invasively obtained fetal cell-free DNA and of exome sequencing from prenatal samples obtained via chorionic villus sampling or amniocentesis.