Research led by the Murdoch Children’s Research Institute (MCRI) has reported that their novel newborn genetic screen may be feasible and reliable to test for three rare genetic disorders simultaneously.
The research, led by Professor David Godler from the MCRI, developed a method to screen for Prader Willi, Angelman and Dup15q simultaneously from a sample taken through the commonly used ‘heel prick’ test.
The study, published in the Journal of the American Medical Association (JAMA) Network Open, reported that the team’s novel test might pave the way for the three chromosome 15 imprinting disorders to be added to the newborn bloodspot screening programs (heel prick test) for the first time.
The mechanism of the test was based on a screening method called Methylation Specific-Quantitative Melt Analysis (MS-QMA), with many of its publications associated with its uses as a diagnostic tool for Fragile X.
Imprinting disorders can be caused by epigenetic mutations where specific areas of genes are silenced and ineffective by DNA methylation, which are chemical markers added to affected areas of the gene.
The three disorders all have different amounts of methylation at the same affected section on chromosome 15. The one-step MS-QMA test then screens for the three syndromes simultaneously by looking at the number of chemical markers added to the affected gene, which are normally not present at such high or low levels in children without these disorders.
Once put to action, the test potentially allows for an earlier diagnosis and treatment of disorders that normally go undiagnosed for the baby’s first year.
Prader Willi, Angelman and Dup15q can lead to varying degrees of intellectual disability, autism, behavioural problems, seizures and or severe obesity.
The three disorders currently affect about 135 newborns per year in Australia but are currently not included in newborn screening programs and often go undiagnosed in the baby’s first year.
Godler said that the key reason why these disorders were not included in current newborn screening programs was the lack of a test with low laboratory costs that could work at a population scale.
“Tests are currently only performed on those suspected of having these disorders, and only if features are recognised by a child’s doctor and subsequently referred for appropriate testing,” he said.
“This is not the case with newborn screening where testing is performed on all newborns before symptoms become apparent.”
The MCRI study, however, has confirmed that the method could be delivered at a large scale for a low cost through standardised newborn ‘heel prick’ tests.
A newborn screening followed by early interventions may benefit babies affected by these conditions. For example, for those affected by Prader Willis, a diagnosis in infancy allows for earlier initiation of growth hormone treatment to improve long-term growth. Early interventions for Angelman and Dup15q could also reduce medical costs and stress and anxiety experienced by families.
The Victorian State Government provided a $100,000 grant to MCRI as part of the 2018 Victorian Medical Research Acceleration Fund to support the development of the new screening method for rare disorders.
Medical Research Minister Jaala Pulford said that the researchers are “world-class and changing lives every day with discoveries like this screening test that will help children reach their full potential.”
Researchers from the Royal Children’s Hospital, the University of Melbourne and international research institutes also contributed to the study.
JAMA Network Open is an international, peer-reviewed, open access, the general medical journal that publishes research on clinical care, innovation in health care, health policy, and global health across all health disciplines and countries.