Identifying the ON/OFF signals that regulate certain genes may help detect the risk of cerebral palsy in infants, allowing access to critical early interventions, according to researchers.
The study from Australia, “Epigenome-wide analysis in newborn blood spots from monozygotic twins discordant for cerebral palsy reveals consistent regional differences in DNA methylation,” was published in the journal Clinical Epigenetics.
Cerebral palsy is caused by damage or alterations to the brain function that may occur in different stages of development — prenatal, perinatal, or early postnatal periods.
Fewer than half of affected children are identified before they turn 1, and only three-quarters are identified before age 2. This delay in diagnosis may prevent access to crucial early interventions, emphasizing the need for improved diagnostic tests.
DNA methylation is a process that regulates genetic readout, working as an ON/OFF signal that tells genes whether or not to produce proteins.
This mechanism is known to be involved in tissue differentiation during early development and neurocognitive function and behavior, with several studies addressing its role in brain disorders such as schizophrenia, bipolar disorder, and Alzheimer’s disease.
Supported by these observations, researchers at Murdoch Children’s Research Institute in Australia questioned whether DNA methylation patterns could help predict early risk of cerebral palsy.
The team evaluated DNA methylation profiles of newborn blood spots collected routinely at birth from 15 identical twin pairs of whom only one child had been diagnosed with cerebral palsy.
Identical twins share the same genetic code, which means that if one child develops a disease and the other does not, it is most probably due to non-shared environmental factors. These may even include intrauterine differences, such as shape or structure of the umbilical cord or placenta.
Comparing the DNA methylation profiles of the infants with cerebral palsy to their healthy siblings, the team identified about 25 genes that were different ON or OFF. Many of these genes were linked to immune responses and inflammation.
In addition, siblings with cerebral palsy had altered DNA methylation patterns regulating the LTA gene, which provides instructions for an important mediator of inflammation and brain development.
“This research is helping us understand more about the genes whose disturbance is associated with cerebral palsy,” Jeffrey Craig, PhD, associate professor at Deakin University’s School of Medicine and senior author of the study, said in a press release.
“By studying ‘epigenetic’ [DNA methylation] marks influenced by the early environment in the womb, we can predict which babies will develop cerebral palsy, enabling early intervention to help lessen the symptoms of this condition.”
The team will explore the potential of DNA methylation patterns to detect infants at risk of cerebral palsy and will collaborate with researchers at the University of Adelaide, Australia, to identify the genetic causes underlying this condition.
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