How to Tackle the "VUS"
Description
In this presentation we will share cases that illustrate how to tackle the interpretation of “variants of uncertain significance” in the neurogenetics clinic.
Neurogenetics and Gene Therapy*
Date: September 14, 2025
Time: 3:30 pm to 5:00 pm
Track: Cross-Cutting Special Interest Group (SIG)
Session Description
This program planned by the Neurogenetics special interest group focuses on current and future approaches to uncovering the full genetic contribution to disease but also leveraging our understanding of neurogenetics for new precision therapies. Sequencing in tens of thousands of individuals with neurological disease over the last decade has resulted in our current appreciation of the prevailing genetic contribution to neurological disease. However, this picture is complex, with most rare neurological conditions being monogenic in nature, while more common disorders, especially later-onset neurodegenerative disease, are rarely monogenic and more often complex with multiple variants contributing to risk. In this session we will discuss strategies for resolving variants of uncertain significance (VUS). VUS are variants where we lack sufficient information to define as either disease-related or benign and are the most common result of clinical genetic testing for rare disease. In addition, we will discuss the X chromosome, oft ignored in genetic studies, and the role of genetic variants in neurodegenerative disease. These two talks will thus focus on redefining (VUS) and defining (X chromosome) genetic causes of neurological disease. We will also present new RNA targeting therapies in myotonic dystrophy, highlighting how understanding genetic and molecular pathophysiology can lead to new therapies.
Learning Objectives
At the conclusion of this session, attendees should be able to:
- Use multiple strategies to resolve VUS.
- Discuss the role of X chromosomal variants in neurodegenerative disease.
- Assess the potential for gene-targeting therapies in patients with rare neurogenetic conditions.
Speakers
- (Speaker) Xilma Ortiz-Gonzalez, MD, PhD
- (Speaker) Bryan Traynor, MD, PhD, FANA
- (Speaker) Samuel Carrell, MD, PhD
The X-Files: Decoding Chromosome X in Neurodegenerative Disease
Description
This presentation will focus on Chromosome X’s role in neurodegenerative diseases, highlighting genetic influences and potential therapeutic targets.
Speakers
Genetic Therapies for Myotonic Dystrophy
Description
This presentation will discuss the active clinical and pre-clinical development of genetic treatments for myotonic dystrophy.