Researchers at the HudsonAlpha Institute for Biotechnology have pinpointed a previously unknown cause of a serious seizure disorder most common in babies, potentially opening the door to new diagnostic and treatment options for infants that show signs of epilepsy.
They found the genetic cause hidden in the SCN1A gene, one of the most heavily studied genes for seizure disorders. The discovery offers an end to the diagnostic odyssey for affected patients, but it also reveals a genetic mechanism for disease that could uncover the cause of other genetic disorders that are not currently well understood.
Scientists in Greg Cooper’s Lab at HudsonAlpha, along with collaborators from across the country, published their findings in the American Journal of Human Genetics. They identified a variant that cues a poisonous piece of genetic code, called a poison exon, to be included in the final instructions for making a crucial protein. When the poison exon is incorporated, it prematurely cancels the protein’s production, which disrupts neural function leading to seizure disorders.
The lab found the mutation on the SCN1A gene after performing whole genome sequencing for a patient that showed symptoms of a disease called Dravet Syndrome, a serious seizure disorder that most commonly appears in infants. This particular variant would not show up on any of the more common genetic tests and it was only identified because the entire genome was sequenced.
After this initial discovery, the Cooper Lab contacted collaborators about the potential for more patients with the same variant. A team of scientists, including the University of Alabama at Birmingham’s Martina Bebin, MD; the University of Washington’s Heather C. Mefford, MD, PhD; and Northwestern University’s Gemma L. Carvill, PhD, was able to assemble enough cases to link the discovered variant to Dravet Syndrome and other patients with closely linked symptoms.
The initial patient that brought the variant to the Cooper Lab’s attention was enrolled in HudsonAlpha’s Clinical Sequencing Exploratory Research (CSER) project, which is aimed at identifying the genetic causes of undiagnosed conditions and funded by the National Institutes of Health.
Bebin said of the patient, “This particular subject that we identified in the NIH CSER project has done extremely well. Initially, they had several prolonged seizures yearly which required treatment at the local ER. It was a frightening experience for the family.” She added that the patient loves school, has been off seizure medication for more than three years and takes a keen interest in sports.
“The family is very grateful to understand the SCN1A diagnosis and their child has done so well,” emphasized Bebin.
“We’re grateful for the families who participated in this research, and excited that the results may offer some clinical benefits to them,” said Greg Cooper, PhD, faculty investigator at HudsonAlpha. “But we’re also excited to have figured out a whole new place to look for genetic variants capable of causing disease.”
By discovering that genetic variation in “poison” exons disrupts crucial protein processes in the developing brain, Cooper’s lab and collaborators from across the country have created a blueprint for future efforts to discover the molecular causes of other genetic diseases and potentially develop treatments for them.
About HudsonAlpha: HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to developing and applying scientific advances to health, agriculture, learning, and commercialization. Opened in 2008, HudsonAlpha’s vision is to leverage the synergy between discovery, education, medicine, and economic development in genomic sciences to improve the human condition around the globe. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. The state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. HudsonAlpha has become a national and international leader in genetics and genomics research and biotech education and includes more than 30 diverse biotech companies on campus. To learn more about HudsonAlpha, visit hudsonalpha.org.