To effectively treat a disease, doctors must first identify its root cause. This identification is complex when it comes to epileptic developmental encephalopathies (EEDs), conditions that affect 1 in 590 children and involve more than 825 genes.
These rare conditions, of genetic origin, are characterized by developmental delay, generalized epilepsy, intellectual disability and autism spectrum disorder (ASD).
Current diagnostic methods can clinically identify the root cause, or etiology, of approximately 50% of EEDs, with identification of causes helping to guide physicians toward appropriate care. One of the lead authors, Dr. Heather Mefford, of the St. Jude Center for Pediatric Neurological Disease Research adds, “Only half of patients with EED are diagnosed. Half of patients who do not receive a diagnosis will not only be unable to get gene-specific recommendations and treatment but will also be unable to connect with other families whose children also have mutations in that same gene “.
The etiology of half of EED thus remains unresolved.
The study demonstrates the value of DNA methylation patterns or “epigenetic signatures” or “episignatures” in identifying the root cause of EEDs, showing that methylation of specific genes can help identify the source genes of EEDs.
- When a child is diagnosed with EED, linking the encephalopathy to a specific gene may allow the doctor to provide appropriate treatment or control the symptoms of the disease.
- 80% of identifiable EEDs can be explained by 27 genes and current tests do not take into account the non-coding part which regulates gene expression. Thus, DNA methylation, one of the main factors of gene expression, therefore offers a solution.
The research is therefore focused on epigenetics, i.e. these changes in the expression of genes linked to DNA methylation. The closer examination of individual methylation cases, called rare methylation analysis, allows here to identify
an underlying cause of the disease that “eventually manifests itself in an episignature.”
In other words, analyzing these rare methylation events helps identify the cause of the disease.
Exploring these rare methylation events using the latest DNA sequencing technologies has directed researchers toward regions of DNA that are not commonly evaluated, providing the answer for these unsolved cases.
The team was thus able to identify:
- the causal etiologies of 2% of EED cases previously unidentified.
It is therefore an important step in identifying the etiology of these rare cases but also of the interest in the study of epigenetics to elucidate the source genes of other rare diseases.
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