Lab-grown 'mini eyes' shed light on blindness in rare genetic disease

CHOP researchers discover genetic variant linked to early childhood epilepsy

Newswise – Philadelphia, November 30, 2022 – Researchers at the Children’s Hospital of Philadelphia (CHOP) have discovered a specific genetic variant in SCN1A, the most common genetic epilepsy, which results in early onset epilepsy, with clinical features distinct from other epilepsies. The researchers also identified a potentially effective treatment strategy. The results were recently published in the journal Epilepsy.

Most genetic variants in SCN1A are associated with Dravet syndrome. Dravet syndrome is a form of genetic epilepsy that is characterized by seizures that begin in the first year of life, as well as differences in child development and characteristics of autism spectrum disorders. In these cases, there is a loss-of-function variant of SCN1A, which means that the resulting protein is not able to perform its normal functions. However, this study focused on a gain-of-function variant of SCN1Ameaning that the resulting protein performs additional functions in a way that may be harmful.

“This genetic change does the exact opposite of what it should, which in turn causes a peculiar clinical presentation,” said study lead author Ingo Helbig, MD, a pediatric neurologist with the Division of neurology and co-director of the Epilepsy Neurogenetics Initiative. (MOTOR) to CHOP. “A better understanding of what this variant does is essential for us to determine which treatments to choose for affected patients.”

In this study, researchers used diagnostic tests to identify four patients with an identical gain-of-function variant in SCN1A. All four patients presented with early developmental and epileptic encephalopathy (DEE), characterized by a combination of seizures and developmental delays. In these specific cases, patients presented with focal tonic seizures, which are seizures that cause the body to stiffen in a specific area, and additional types of seizures beginning within the first few weeks of life. The study also found that patients with this recurrent gain-of-function variant in SCN1A– disease-related epilepsies had an earlier onset of their disease compared to patients with loss-of-function variants.

Additionally, the study found that oxcarbazepine, an antiepileptic drug for children and adults, can help patients. One of the patients responded to treatment with the drug and the variant showed sensitivity to the drug.

“Our results may explain why we previously diagnosed some patients with atypical Dravet syndrome, because the early onset of symptoms associated with this gain-of-function variant allows us to correctly distinguish these cases,” said the first author of the paper. ‘study. Jérôme Clatot, PhD, director of the ENGIN Ion Channel/Electrophysiology Core at CHOP. “We hope to raise awareness of this and other potential gain-of-function variants, particularly if common anti-epileptic drugs may be able to help them.”

This study was supported by the Hartwell Foundation Individual Biomedical Research Award and National Institute of Health National Institute of Neurological Disorders and Stroke Fellowships K02 NS112600, U54 NS108874 and R01 NS110869 and the Burroughs Wellcome Fund Career Award for Medical Scientists.

Clatot et al.SCN1A gain-of-function mutation causing early-onset epileptic encephalopathy. Epilepsy. Online October 26, 2022. DOI: 10.1111/epi.17444.

About Children’s Hospital of Philadelphia: A non-profit charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its longstanding commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and launching major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children all over the world. Its pediatric research program is one of the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty and surgical care centers, emergency and community hospital alliances across Pennsylvania and New Jersey. , as well as a new inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have earned The Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit

#CHOP #researchers #discover #genetic #variant #linked #early #childhood #epilepsy

Leave a Comment

Your email address will not be published. Required fields are marked *