Genetic counseling. This month, we celebrated DNA day, a successful fundraiser through Love for Liam, and the acceptance of our genetic counseling assistant (GCA), Rahma Ali, into the Emory University Genetic Counseling Training Program. On top of that, the Center for Epilepsy and Neurodevelopmental Disorders (ENDD) opens soon and we’ve been actively recruiting new GCAs and interviewing new genetic counselors (GCs). All of this has reminded our team of the vital function of our GCs both on our research and clinical teams. And, it has reminded our GC team of why we pursued this field and why we love neurogenetics in particular. As our lab expands, we are dedicating more blog posts to highlighting different team members and roles, and this week, we celebrate GCs as they share the greatest, hardest, and most exciting parts of being a GC, especially in neurology.
STXBP1 – here is what you need to know in 2023
STXBP1. Today is the first day of the 1st European STXBP1 Summit and Research Roundtable, held from May 16-18th in Milan, Italy. This meeting is bringing together voices from academia, industry, organizations, and family foundations to discuss the current state of research – spanning from preclinical efforts investigating mechanisms of disease to moving towards the clinic and the future therapeutic landscape. In 2023, it feels like an understatement to say that STXBP1 is on the map. In spirit of the ongoing momentum in the field, we wanted to refresh the gene page and outline three emerging frameworks to think about STXBP1.
The Queen of the Biorepositories
Biospecimens. From the first advents of clinical neuroscience, scientists have been fascinated by biospecimen classification and storage. The immortal images from Ramon y Cajal to the staining done by Golgi have illustrated that biospecimens are parallel to the discoveries seen in clinical neuroscience. As we move to the 21st century, we may not be all that different from the forbearers of Neurology. Here is a post starting from the origins of the biorepository and leading up to the relevance of biorepositories today.
The human pangenome and the flavor of epilepsy variant interpretation
Reference. Today, the human pangenome was announced, the first reference of the human genome that systematically includes a cohort of genetically diverse individuals. The human genome, once thought to be a linear reference, is now a graph with nodes and edges. I came across the pangenome publications when I was thinking about a comment that I made earlier this week, when I was asked whether people on our team have their own flavor of variant interpretation. Let me share with you how both topics connect. Continue reading
Five novel concepts in epilepsy genetics you need to know in 2023
Framework. Neurogenetics is evolving, and so is the way we think about the connection between genes and seizures. Over the last few years, several new frameworks of thinking have entered the epilepsy genetics sphere that allow us to think about epilepsy genetics with more nuance. This blog post is dedicated to five known or emerging concepts that are evolving alongside our increased understanding of genetic epilepsies. Continue reading
Expanding the spectrum of SNAREopathies – STX1A in epilepsy and neurodevelopmental disorders
SNAREopathies. This post continues the series on SNAREopathies, a group of neurodevelopmental conditions caused by variants in genes encoding components that form the SNARE complex and regulatory proteins. As previously described, the SNARE complex is the molecular machinery driving synaptic vesicle release in the presynapse, which enables communication between neurons. Here, we expand the discussion to the second t-SNARE protein of the SNARE core complex, STX1A, and provide a brief review of the recent paper implicating STX1A in epilepsy and neurodevelopmental disorders.
Love For Liam and the true driving force in epilepsy genetics
Fundraiser. Last Friday, our epilepsy genetics team participated in the Annual Love for Liam fundraiser, which was a golf tournament at the Northhampton Country Club, in Richboro, Pennsylvania. The Love For Liam Foundation was initiated by Heather and Kyle Johnson in memory of their baby boy, Liam, who passed away from a likely genetic epileptic encephalopathy. During the fundraiser, Heather gave one of the most passionate and powerful speeches in support of epilepsy genetics that I have ever heard. I had carried around a sense of “bittersweetness” all day that I had a hard time putting into words. And after Heather’s speech, it clicked: maybe we got it all wrong, maybe we should think about the real driving force in epilepsy genetics slightly differently.
TBC1D24 in 2023 – a mother and researcher’s perspective
TBC1D24. Yes, our last blog post regarding TBC1D24 was published in 2015, but that doesn’t mean we aren’t still thinking about this elusive gene and its wide phenotypic spectrum. Today we provide an update from Joeylynn – a new research coordinator in the Helbig lab, a health care provider, co-creator of the TBC1D24 Family Foundation, and most importantly, the mother of a child with TBC1D24
SNAREopathies in epilepsies and neurodevelopmental disorders
SNARE complex. This is the first post in our series on SNAREopathies – an umbrella term for diseases caused by variants in the soluble NSF attachment protein receptor (SNARE) complex, that is essential for neuronal synaptic vesicle exocytosis in the presynapse. The core SNARE complex comprises a four-helix bundle consisting of two SNAP25 helices, which is encoded by SNAP25, the syntaxin 1 helix encoded by STX1A/STX1B, and the synaptobrevin 2 helix encoded by VAMP2. The complex is regulated by different proteins including MUNC18 encoded by STXBP1, MUNC13 encoded by UNC13A, and synaptotagmin encoded by SYT1 and complexins. Here is an overview of SNAREopathies, with a focus in this post on SNAP25 and VAMP2.
Genomics-driven prediction of multi-omics data across 50,000 people
Multi-omics. An emerging avenue of research for investigating the underlying architecture of human disease is the development of multi-omics approaches. Integration and analysis of large-scale data generated from genome sequencing alongside other -omics technologies including transcriptomics, proteomics, and metabolomics, enable a more comprehensive and nuanced insight into biological systems that underlie disease. However, in contrast to genomic data, the generation of multi-omics data remains expensive, time-consuming, and is typically limited in large-scale population studies. In a recent publication, Xu and collaborators developed a model predicting >17,000 multi-omic traits from genomic profiles across 50,000 people. Here is a brief review of their paper, with a focus on the relevance of developing multi-omics resources in 2023.
