Rare diseases are usually genetic in origin, so descendants inherit them. Knowing the genetic cause responsible for these pathologies can help carriers plan future pregnancies and use techniques such as embryo selection to avoid transmission. Currently, prenatal diagnostic techniques are mostly based on DNA, but RNA sequencing has been found to improve diagnostic efficiency by 10-36%, although this type of study has not focused on prenatal diagnosis.
A group of researchers from the University of Hong Kong (HKUMed) have collected cells from amniotic fluid during weeks 16 to 24 of pregnancy and used them as a new type of sample for RNA sequencing in prenatal diagnosis. This is the first study to demonstrate the potential clinical utility of RNA sequencing of amniotic fluid cells, and its results have been published in the journal npj Genomic Medicine.
Precision medicine for cases of genetic alterations
A baseline for the gene expression profile of amniotic fluid cells was established by RNA sequencing in more than 50 amniotic fluid samples and the researchers found that the number of well-expressed genes in amniotic fluid cells it was comparable to other tissues that are commonly used for genetic diagnosis in different categories of diseases. The researchers also compared RNA sequencing data from four fetuses suffering from structural congenital malformations with the established baseline to detect potential outliers.
Identifying the genetic cause enables precision medicine, such as preimplantation genetic diagnosis for those with a family history
Further analysis in collaboration with the Technical University of Munich (Germany) showed that outliers can be identified in the genes associated with the corresponding structural congenital anomalies in all four affected fetuses. Identifying these outliers provides further evidence at the RNA level to aid diagnosis. The research findings can make a significant contribution to addressing undiagnosed rare diseases in Hong Kong.
This is the first time they have found evidence that RNA sequencing of amniotic fluid cells has potential clinical utility in prenatal diagnosis. Identification of the genetic cause enables precision medicine, such as personalized clinical management and preimplantation genetic diagnosis for those with a family history.
.
