By Clinical Research News Staff 

October 3, 2024 | A pioneering study led by Dr. Lachlan Jolly at the University of Adelaide’s Neurobiology Research Group is transforming genetic diagnostics by resolving variants of uncertain significance (VUS) using skin samples. Many patients with VUS lack a definitive diagnosis because RNA from disease-causing genes often can't be extracted from accessible tissues like blood or skin.  

The PERSYST study, Pathogenic Evaluation of Recalcitrant Variants by Systematic Transactivation, is a national program in Australia actively recruiting individuals living with a medical condition caused by VUSs within rare silent disease genes. Jolly's team is using innovative techniques—transactivation and transdifferentiation—to activate these "silent genes" in skin fibroblasts, enabling researchers to retrieve the necessary RNA for diagnosis. 

This approach is crucial for patients, as it opens access to clinical trials and precision therapies targeting rare genetic diseases. Approximately 13,000 clinical trials globally are focused on treatments for conditions tied to genetic mutations, but participation requires a solid genetic diagnosis. Jolly’s work aims to provide this diagnosis by unlocking RNA from hard-to-access genes, particularly those linked to brain disorders. The team has successfully activated over 230 silent genes, a major step in enabling RNA sequencing and variant classification. 

The PERSYST study is part of a broader effort to provide functional RNA-based evidence for VUSs, offering new hope to patients. With this research, individuals who previously faced diagnostic uncertainty could gain access to life-changing trials and treatments. For more details on this groundbreaking study, read the full article at Diagnostics World News.