Clinical use of EpiSign proven for diagnosing rare heritable disorders

A study led by researchers at Lawson Health Research Institute (Lawson) provides clinical validation of EpiSign, a molecular genomics test that diagnoses rare, heritable neurodevelopmental conditions. 

Invented at Lawson by Dr. Bekim Sadikovic, the diagnostic test uses machine learning to analyze the EpiSign Knowledge Database. This database compiles information on rare genetic diseases using laboratory analyses of the epigenome from patients with suspected genetic abnormalities. The epigenome is a process that can change the expression of a gene without changing the gene sequence. 

“Using 211 blood samples, we measured test performance and diagnostic yield in 207 subjects from two different cohorts,” explains Dr. Sadikovic, lead researcher at Lawson and Scientific and Clinical Director of the Verspeeten Clinical Genome Centre at London Health Sciences Centre (LHSC). The targeted cohort were subjects with previous genetic findings that were ambiguous or inconclusive. The screening cohort were those with clinical findings consistent with hereditary neurodevelopment syndromes but with no previous genetic findings.  

“Of the 207 subjects tested, 57 were positive for a diagnostic episignature including 48 in the targeted cohort, and 8 in the screening cohort. Only four remained inconclusive after EpiSign analysis,” says Dr. Sadikovic. “This gives us strong evidence for the clinical use of EpiSign, as well as the ability to provide conclusive findings in the majority of subjects tested.” 

While currently there are limited treatment options associated with many of these conditions, providing a diagnosis can help physicians better predict the course of the disease, and allows for better planning and support for the patient. EpiSign is the only test in the world that has been clinically validated for testing these kinds of genetic disorders. 

“Patients with rare diseases often wait years and undergo numerous exams and tests before receiving a correct diagnosis, if one is found at all,” says Matthew Tedder, PhD, staff scientist at the Greenwood Genetic Center, one of the EpiSign clinical testing laboratories. “EpiSign provides an additional high-yield diagnostic tool for clinicians to include in their evaluation of patients with undiagnosed diseases, providing better medical management for patients and hope for their families.”  

The study, “Clinical epigenomics: genome-wide DNA methylation analysis for the diagnosis of Mendelian disorders", is published in February’s Genetics in Medicine and was completed in collaboration with the Greenwood Genetic Center and the University of Amsterdam. 


Image provided by Greenwood Genetics Center.