Novel prenatal diagnosis: RNA sequencing of amniotic fluid cells

A clinical research team from the University of Hong Kong (HKUMed) used amniotic fluid cells obtained during 16-24 weeks' gestation as a new sample type for RNA sequencing for prenatal diagnosis to help more families with tailored clinical management
.
This is the first proof-of-concept study
demonstrating the potential clinical application of RNA sequencing of amniotic fluid cells.
The findings have been published in the journal npj Genomic Medicine
.

Rare diseases are usually hereditary
.
According to the team's previous research, although individual are rare, the proportion of collective rare diseases in the Hong Kong population is 1 in 67
.
Finding genetic causes of rare diseases can provide accurate counseling for better clinical management and future pregnancy planning, and is critical
to patient support.
Current prenatal diagnostic techniques are largely DNA-based, with a large proportion (60-70%) remaining undiagnosed, leading to clinical uncertainty and parental anxiety
.

RNA sequencing has recently been found to increase diagnostic rates by 10% to 36%; However, none of these studies focused on prenatal diagnosis
.
In addition, despite the existence of well-established large databases that catalog gene expression profiles of different tissues in adults, similar public datasets
reflecting amniotic fluid cells in embryonic and fetal stages are lacking.
Therefore, further research
on prenatal RNA sequencing is warranted.

The team demonstrated the potential clinical application value
of RNA sequencing of amniotic fluid cells.
By RNA sequencing of more than 50 amniotic fluid samples, a baseline
of gene expression profiles of amniotic fluid cells was established.
Establishing a gene expression profile is a critical step
in applying RNA sequencing to the currently selected clinical diagnostic workflow.

The researchers found that the number of well-expressed genes in amniotic fluid cells is comparable to that of other clinically accessible tissues and is commonly used for genetic diagnosis
of different disease classes.
The team also compared RNA-sequencing data from four affected fetuses with structural congenital anomalies to established baselines to detect potential outliers
.

In collaboration with the Technical University of Munich, Germany, the bioinformatics pipeline is used to enhance the detection of outliers for subsequent analysis
.
Further in-depth studies have shown that in all four affected fetuses, outliers
can be identified in genes associated with the corresponding congenital structural abnormalities.
Identifying outliers can provide more evidence at the RNA level to aid diagnosis
.

The results of this study have important implications
for addressing undiagnosed rare diseases in Hong Kong.
This is the first time in the literature that RNA sequencing of amniotic fluid cells offers potential clinical applications
in prenatal diagnosis.
With the determination of genetic causes, it is possible to carry out tailored clinical management and precision medicine
such as preimplantation genetic diagnosis for families with a family history.

Courtesy of The University of Hong Kong