New blood test has clinical utility for patients with a broad range of constitutional disorders, as well as ID and congenital anomalies.
GREENWOOD, SC – Greenwood Diagnostic Laboratories at the Greenwood Genetic Center, in collaboration with London Health Sciences Centre (LHSC), announce
the launch of a new diagnostic test focused on disease-specific epigenetic signatures. The test, EpiSign, which is performed on a peripheral blood
sample, analyzes DNA methylation patterns of the genome to establish a diagnosis or help resolve variants of uncertain significance (VUS) found through
To date, combined efforts have identified unique methylation patterns, known as epigenetic signatures, for 19 genetic disorders including CHARGE syndrome,
Cornelia de Lange syndrome, Down syndrome, Kabuki syndrome, Sotos syndrome, Williams syndrome, ATRX syndrome, autosomal dominant cerebellar ataxia
with deafness and narcolepsy (ADCADN), BAFopathies (Coffin-Siris syndrome , Nicolaides-Baraitser syndrome, Chr6q25del), Claes-Jensen syndrome, Genitopatellar
syndrome, Floating Harbor syndrome, ADNP-related syndrome/Hellsmoortel-VanDerAa syndrome, and Chr7q11.23dup.
EpiSign uses an Illumina Infinium Methylation EPIC bead chip array to analyze DNA methylation at hundreds of thousands of loci across the genome. A computational
model has been developed to interpret the data and provide the concurrent identification of the syndromes that have been associated with unique epigenetic
signatures. The list of syndromes for which this test is useful continues to grow.
“Current diagnostic technologies such as microarray and whole exome sequencing are not able to assess non-coding and more complex variants, and cannot
provide information on epigenetic changes,” said Bekim Sadikovic, PhD, DABMG FACMG, Division Head, Molecular Diagnostics, LHSC; and Associate Professor,
PaLM, Western University, who leads the epigenetic signature research. “This technology provides a new level of analysis beyond the genome.”
EpiSign data can also detect imprinting defects as well as altered methylation patterns in trinucleotide repeat expansions, making it useful for patients
with a suspected diagnoses of disorders such as Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome and Beckwith-Wiedemann syndrome.
“The power of this technology lies in the ability to resolve diagnoses for patients with clinical uncertainty, some of whom have unclear phenotypic features,
and others who may have a VUS in an associated gene,” said Mike Friez, PhD
, FACMG, Director of
Greenwood Diagnostic Laboratories at the Greenwood Genetic Center.
Epigenetic variants have also been found with increased frequency in patients with unexplained intellectual disability (ID) and/or congenital anomalies
(CA), and they have been shown to influence gene expression similarly to sequence variants.
Friez noted that achieving an accurate diagnosis for conditions involving ID and/or CA can be challenging, “These phenotypes are often associated with
variable, complex and overlapping features. Even with advanced sequencing and powerful array technology, the current diagnostic yield for these patients
is between 42-62%, leaving many without a clear diagnosis. EpiSign is another tool now at the clinician’s disposal to help end the diagnostic odyssey
for many families.”
Sadikovic will present an update on epigenetic signatures at the American College of Medical Genetics and Genomics Annual Meeting in Seattle on Thursday,
April 4th at 4:15pm in Meeting Room 6E.
Greenwood Diagnostic Laboratories will begin accepting clinical samples for EpiSign on April 8, 2019. For more information visit www.ggc.org/EpiSign
About London Health Sciences Centre
London Health Sciences Centre has been at the forefront of medicine in Canada for 144 years and offers the broadest range of specialized clinical services in Ontario. Building on the traditions of its founding hospitals to provide compassionate care in an academic teaching setting, London Health Sciences Centre is home to Children’s Hospital, University Hospital, Victoria Hospital, the Kidney Care Centre, two family medical centres, and two research institutes – Children’s Health Research Institute and Lawson Health Research Institute. As a leader in medical discovery and health research, London Health Sciences Centre has a history of over 70 international and national firsts and attracts top clinicians and researchers from around the world. As a regional referral centre, London Health Sciences Centre cares for the most medically complex patients including critically injured adults and children in southwestern Ontario and beyond. The hospital’s nearly 15,000 staff, physicians, students and volunteers provide care for more than one million patient visits a year. For more information visit