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Providing patients with a swift and precise genetic diagnosis may lead to rational therapeutic choices and insights into the prognosis and recurrence risk of the disorder within a family. However, only a third of the patients with neurodevelopmental disorders of presumed genetic origin receive a definitive diagnosis after routine diagnostic procedures. Genome sequencing now has the potential to be implemented as first-tier genetic test for patients with neurodevelopmental disorders.
Researchers Van der Sanden, Schobers, Corominas Galbany and colleagues showed that genome sequencing is ready to be implemented in routine diagnostic genetic testing with the potential to increase the diagnostic yield and also reduce the time that is needed to provide a patient with the genetic diagnosis. The research group, led by Lisenka Vissers from the department of Human Genetics, published the results in the European Journal of Human Genetics last month.
They performed both genome sequencing and the standard-of-care, consisting of exome sequencing supplemented with additional genetic tests, for a cohort of 150 neurodevelopmental disorders patients and their unaffected parents. The primary outcome of the study was the diagnostic yield, calculated from disease-causing variants affecting the coding regions of known neurodevelopmental disorders associated genes. They found a diagnostic yield of 30.0% for the genome sequencing pathway and 28.7% for the standard-of-care pathway. By comparing the individual diagnoses they found that all conclusive diagnoses obtained with the standard-of-care were also identified by genome sequencing. Despite the limited additional diagnostic yield of genome sequencing, it successfully identified all clinically relevant genetic variants in a single test, while the standard-of-care used multiple tests to reach the same conclusions. This suggests that genome sequencing is a more efficient workflow than the current standard-of-care.
Because of the close collaboration of Vissers’ research group with the laboratory of genome diagnostics, these results could contribute to the implementation of genome sequencing in routine genetic testing soon.
Read the study here: The performance of genome sequencing as a first-tier test for neurodevelopmental disorders | European Journal of Human Genetics (nature.com)
van der Sanden, B. P., Schobers, G., Corominas Galbany, J., Koolen, D. A., Sinnema, M., van Reeuwijk, J., ... & Vissers, L. E. (2023). The performance of genome sequencing as a first-tier test for neurodevelopmental disorders. European Journal of Human Genetics, 1-8.
