SALT LAKE CITY--(BUSINESS WIRE)--Lineagen, Inc., an innovative genetics diagnostics company focused on complex neurodevelopmental disorders, announced today the publication of a major study revealing a significant genetic contributor to epilepsy in Wolf Hirschhorn syndrome. The study was the result of a unique collaboration between academic research institutions, a patient advocacy group known as the 4p- Support Group and Lineagen. Academic researchers hailed from the University of Utah, the Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry (Pisa, Italy), the University of Minnesota and the University of New Mexico.
Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving variable size deletions of the short arm of chromosome 4. Approximately 90 percent of individuals with WHS experience seizures. These seizures can be severe during the child’s first years of life, and can seriously affect both quality of life and cognitive development. To study the genetic correlates of seizure susceptibility in WHS, the research team used Lineagen’s FirstStepDx PLUS®, a high-density chromosomal microarray platform that is optimized to detect genomic changes associated with autism and neurodevelopmental disorders.
This is the first academic publication involving the use of this optimized platform on a cohort of individuals to identify a potential candidate gene for epilepsy. By correlating the size and location of chromosome 4p deletions in 48 individuals battling WHS with their seizure symptoms, the team identified a new genetic region for seizure susceptibility, located near the 4p terminus. This region includes a potential candidate gene, phosphatidylinositol glycan anchor biosynthesis gene G (PIGG), for seizure susceptibility. It is a member of a gene family also involved in congenital disorders of glycosylation. This finding may additionally relate WHS to another seizure-related disorder, Dravet syndrome, and also identify a new potential therapeutic target for these conditions.
“What we found underscores the importance of using high-resolution chromosomal microarray as a first-tier test for individuals with genetic disorders such as WHS that underlie much of developmental delay and autism spectrum disorders,” stated Dr. Robert Wassman, chief medical officer for Lineagen. “The region we identified, as well as secondary genetic changes that frequently occur in WHS, can be missed using alternate detection methods. Chromosomal microarray is key in providing the best medical care for these individuals, as well as for the identification of novel disease correlations and possible therapeutic targets for other genetic syndromes, including 15q duplication syndrome.”
“We are extremely pleased to have partnered with Lineagen to further this exciting research, which holds great promise in advancing the understanding of Wolf-Hirschhorn syndrome," said Amanda Lortz, executive director of the 4p- Support Group. “Families of individuals with Wolf-Hirschhorn are in desperate need of information on the natural history, long-term prognosis and optimal management in caring for their loved one. The 4p- Support Group is acutely aware of the current deficiencies in medical knowledge about the complexities of Wolf-Hirschhorn syndrome, especially the problematic seizures in so many patients. Our organization is dedicated to advancing research on this complex condition, so we greatly appreciate Lineagen’s involvement. Through this partnership and our members’ ongoing participation and support, we sincerely believe that now we are one step closer to better seizure control in Wolf-Hirschhorn syndrome, and to greater understanding of other neurodevelopmental conditions."
Dr. Michael Paul, chief executive officer for Lineagen, concurred: “This study highlights the value of partnership with top academic institutions and advocacy organizations to advance our understanding of the underlying genetic cause of developmental disorders, including Wolf-Hirschhorn syndrome. Studies like these, utilizing our unique and optimized high-definition CMA, will ultimately lead to more genetic diagnoses, improved treatment options for patients, peace of mind for families and hopefully, targeted therapies in the near future.”
Future Lineagen studies will involve the development of new computational and statistical methods to identify more genetic correlates of WHS traits, and to further characterize the mechanism of seizures based on this study’s findings. Such studies aim to identify potential treatments for many of the medical issues faced by individuals with WHS.
Results from Lineagen’s study were published in the current issue of Journal of Medical Genetics; a copy of the article can be accessed here: http://jmg.bmj.com/cgi/content/full/jmedgenet-2015-103626. A short blog post about this article can be found here: http://blogs.bmj.com/jmg/2016/01/08/a-genetic-region-associated-with-seizure-susceptibility-is-identified-in-wolf-hischhorn-syndrome/.