February 24th is international SCN2A awareness day! This week we recognize the individuals and families affected by SCN2A and share some insights into new science coming out of our lab.
What is SCN2A?
Two different presentations of SCN2A: In the past few years, we have learned more about different possible presentations (which scientists often call "phenotypes") of SCN2A.
What is it like to research SCN2A? Perspectives from our trainees
Wes Ganz, University of Washington: My time as a research assistant began at the SCN2A conference in Seattle, and I could not be more thankful for this opportunity. The SCN2A conference significantly influenced my lens as a researcher. Particularly, I want the science I contribute to be beneficial for the population that is being researched. I have carried this philosophy forward in all research that I am involved in. Whenever working with SCN2A participants and their data, I am constantly reminded of the families and carriers that will potentially benefit from this work. I could not be more grateful to be contributing to this fascinating research and contributing to the SCN2A community.
Nicole Friedman, University of Alabama: For the last few years before starting graduate school at the University of Alabama, I worked as a research assistant at the Fragile X Research and Treatment Center at Cincinnati Children's Hospital. In this role, I had the pleasure of getting to know some of the most amazing FXS kiddos, teens, adults, and many of their extended families. Our team was extremely involved with the National Fragile X Foundation at both the local and national level, so I attended many events hosted by the local family group as well as 2 International Fragile X conferences. I really grew close to so many families and felt honored to be welcomed as a part of their tight knit community. My experience with FXS drew me to the B-RAD Lab at UA, where Dr. Hudac is doing really amazing work in rare genetic populations. I am so excited for the opportunity to work with the SCN2A families and expand my knowledge of genetics in the field of neurodevelopmental disorders. I look forward to supporting SCN2A projects this upcoming summer!
What is it like to research SCN2A? Perspectives from our clinicians
Dr. Eva Kurtz-Nelson, University of Washington: It's an honor to research SCN2A--people with SCN2A events are so resilient, and their family members are committed advocates and research partners. We hope our research will help medical and treatment providers give the best care possible to people with SCN2A.
Tell us about your progress on developing EEG biomarkers.
The COVID-19 pandemic created in obstacle in seeing more participants for our BioGENE study, but we are excited to debut some preliminary results related to our resting state biomarker. We submitted an abstract to the International Society for Autism Research (INSAR) looking at underlying brain responses from resting state EEG. Here, we were looking to see if there are differences across spectral frequencies that reflect varying brain states -- with a special focus of looking more at the differences between loss-of-function (LOF) and gain-of-function (GOF) mutations.
How do we know if a variant is LOF/GOF?: To know for certain whether a person's genetic mutation is LOF/GOF, it is important to identify each variant's function using molecular neuroscience and cellular electrophysiology to test what happens in a neuron. We use scalp electrophysiology , which measures ALL the neurons instead of one at a time. Although many variants have been tested and are known to be LOF/GOF, we do not know the status for ALL of our participants. Instead, we work from the assumption that participants with a presentation of infantile epileptic encephalopathy (+IEE or "with IEE") or other disruptive seizures during early development (<12 months of age) may have a GOF mutation. And those that do NOT have IEE (-IEE) may have a LOF mutation.
Study design: Our participants watched screensaver-like videos while we recorded electrical signals using electroencephalography (EEG) using a wet net with over 120 recording locations. We take the raw signal and extract out information related to overall/broad brain states -- delta (deep sleep, slow rhythms), theta (daydreaming, moderate rhythms), alpha (reflection after a task, fast rhythms), and beta (engagement, fastest rhythms).
Study results: We found that:
What does this mean?: Some of these findings relate to other work characterizing brain states in adults with a more broad or "generalized" epilepsy (for instance, see this study from 2000). It is encouraging that the SCN2A participants have distinct profiles relative to our control groups. To feel more confident in our findings, we will continue to add additional participants to our study.
In early August 2019, Dr. Hudac presented at the 3rd Annual SCN2A Family and Professional Conference in Seattle, WA. Watch her talk on "Human Brain Markers in SCN2A" below and check out more of the talks on the FamiliesSCN2A Website.
Check here for updates and news about the B-RAD Lab.