Högskolan i Skövde

Although substantial advancements have been made in genetic testing, several barriers continue to limit patient access, leading to delays in diagnosis, effective treatments, and preventative measures. The NEUROMYODredger-3billion Megaproject End the Diagnostic Odyssey grant offered free whole exome sequencing (WES) to 245 patients with undiagnosed neurodevelopmental or neuromuscular disorders in seven countries: Algeria, Chile, Egypt, France, Mexico, Peru, and Romania. We found pathogenic variants in 79 patients (diagnostic yield 32.24%)—36 neurodevelopmental (43.90%) and 43 neuromuscular (26.38%). Fifty patients harboured variants of uncertain significance (VUS, 20.40%)—14 neurodevelopmental (17.07%) and 36 neuromuscular (22.08%), and 116 patients had negative results (47.34%). NEUROMYODredger helped end the diagnostic odyssey in around 30% of patients, while ongoing functional studies and reanalysis strategies are used in order to reach more diagnoses. In conclusion, a singleton WES approach is valuable in determining the genetic diagnosis of neurodevelopmental and neuromuscular diseases, especially in low and middle-income countries.