May 13, 2021
Here are the introductory comments:
Our talk for today is “Functional Assessment of Missense Variants of SYNGAP1.”
I have the pleasure to introduce today’s speaker professor Kurt Haas.
He is a professor of cellular and physiological sciences at the faculty of medicine at the University of British Columbia.
The primary goal of Dr. Haas’s research is to understand how brain circuits form during early development and how mutations and errors give rise to dysfunctional circuits that underlie common neurodevelopmental disorders such as Autism Spectrum Disorders and Epilepsy.
The distinctive feature of his research approach is the development of imaging tools that combine electrophysiology, genetics and microscope design to see brain neural network activity and growth.
Dr. Kurt Haas is a professor of cellular and physiological sciences at the University of British Columbia and does research at the Centre for Brain Health. His objective is to understand the genetic architecture of autism spectrum disorder (ASD); however, there are thousands of single-nucleotide variants found in ASD genes and most are variants of unknown significance (VUS), making it very difficult to understand.
In his lab, Dr. Haas has identified 57 SYNGAP1 variants and has developed 7 assays to test their structure function. He explains how the data from these assays can create a multi-parametric functional impact score, an unbiased score that takes into account each of the assays with equal weighting. This score showed varying levels of dysfunction for each variant, suggesting that there are multiple mechanisms of dysfunction – SYNGAP1 dysfunction is not solely caused by haploinsufficiency. He closes with goals for the future, including finding more SYNGAP1 variants, as well as clinically assessing individuals with variants of distinct molecular mechanisms of dysfunction.