Researchers at the University of Melbourne have developed a blood test that can analyze thousands of proteins in a single test to search for rare disease markers.
The researchers hope that their test could help to identify children and adults with rare diseases more quickly as these individuals often have to wait for as long as five years before they get a diagnosis.
Currently, babies are screened for a panel of around 38 rare diseases and 26 other conditions using a heel prick test shortly after birth. During the test, a small amount of blood is taken from the baby’s heel and then a genetic test is carried out on the blood to look for mutations linked to the listed conditions.
Other genetic tests, such as whole genome sequencing, are in use in some areas to help diagnose rare disease but are not as widespread as the heel prick test.
Presenting the results of their test at the European Society of Human Genetics conference in Milan, Daniella Hock, a Senior Postdoctoral Researcher at the University of Melbourne, Australia, explained that “around 50% of individuals with a suspected rare genetic disease remain undiagnosed, often due to variants of uncertain significance identified by genomic sequencing approaches.”
The test developed by Hock and colleagues uses peripheral blood mononuclear cells from parents and children with signs of rare diseases and mass spectrometry to look for potentially pathogenic proteins. The researchers have also tested a panel of more than 400 healthy controls to provide a normal standard for the proteins being tested.
So far, the test typically identifies more than 8000 proteins and covers over 50% of known Mendelian and mitochondrial disease genes. The team has managed to provide evidence of pathogenicity in 83% of individuals with known mitochondrial disease.
Notably, the test was able to differentiate between parental carriers and affected children and provide evidence of causation in cases with an unknown mutation.
Advantages of this test over those currently in clinical use include the sheer number of proteins it is able to characterize (over 8000), the fact that it only requires 1 ml of blood from infants and that results can be obtained in less than three days. It also helps to study the functionality of the proteins and can differentiate between carriers and those affected by rare disease in recessive conditions.
Another advantage is that it comes with a reasonable cost. “A recent study carried out in collaboration with the Melbourne School of Population and Global Health revealed that implementing our test in a clinical setting would have a similar cost to that of the current test used to diagnose rare mitochondrial disease, with the advantage that our test can potentially diagnose thousands of other diseases,” said Hock in a press statement.
The test can also help characterize newly discovered pathogenic mutations that are not currently recorded in the literature.
