Study validates clinical utility of EpiSign for diagnosing rare heritable disorders

New diagnostic test developed in collaboration with Clinical Genetics Amsterdam UMC, effective for providing conclusive genetic tests.

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

Developed at Lawson, 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.

“In collaboration with the Amsterdam UMC and the Greenwood Genetic Center we used 211 blood samples to measure test performance and diagnostic yield in 207 subjects from two different cohorts,” explains Dr. Bekim Sadikovic, Lawson Scientist and Head of the Molecular Diagnostics Division at London Health Sciences Centre (LHSC). The two subgroups included the targeted cohort; subjects with previous ambiguous/inconclusive genetic findings, and the screening cohort; subjects with clinical findings consistent with hereditary neurodevelopmental syndromes and no previous conclusive 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 utility 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.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 AmsterdamUMC.