Genetic Diagnosis in ASD: Re-Examining Genome Sequencing Data - Richard Boles MD @Synchrony2022

"High Sensitivity for Monogenic Causal Diagnoses in Autism, Including De Novo Variants Representing Novel Disorders, with Trio Whole Genome Sequencing and Data Reanalysis"
The last decade has seen dramatic improvements in the proportion of the genome clinically sequenced and bioinformatic tools. Rapidly shifting methodologies have complicated sensitivity measurements. To determine the current sensitivity, we analyzed the raw DNA sequencing files on the Variantyx bioinformatics platform for the last 20 autism patients with trio whole genome sequencing (WGS).
Monogenic causal diagnoses (MCD) were provided in 15/20 (75%) cases, including 11 with heterozygous de novo variants. 4/5 patients with seizures received MCDs. Only 7/15 of MCD cases had the variant listed on the laboratory report. The “missed” cases included genes with few (THOC2, SLC41A2) and no prior reports (TRPM2, PGAM5, MTMR4, GRIK1, CD177). Only de novo variants in genes previously associated with autism were labelled as MCD. 3/4 cases without an MCD had inherited variants likely related to disease. Overall, 16/20 (80%) of cases had treatment recommendation(s) based on DNA.
Our results demonstrate high yield of trio WGS for revealing molecular diagnoses in autism that is greatly enhanced by re-analyzing DNA sequencing files. Many are de novo and represent un/under-published conditions that are not within the scope of reporting by clinical laboratories. Genes resulting in autism and epilepsy substantially overlap.
🎥 This talk was part of Synchrony 2022 Online Symposium - 'From Bench to Biopharma', organised by the The BRAIN Foundation
🎥 For more Synchrony 2022 talks and highlights:
• Synchrony Symposium 20...
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Synchrony synchronysympo... is the first and only international symposium on translational research in #autism, that brings together academia, #biotech, pharmaceutical companies and #venture partners from around the world with the mission to improve health and quality of life of people with #autismspectrumdisorder.
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The BRAIN Foundation brainfoundatio... is a 501c(3) non-profit. The founders of BRAIN envision a world where every child and adult on the autism spectrum is healthy, participates fully in education and employment, and has a better quality of life. It aims to catalyze research that results in evidence-based interventions for the disabilities associated with autism, and also results in better medical standard of care.
To accomplish this, it funds impactful research through #philanthropy and our network of partners in the venture, corporate, and grassroots community.