Whole-exome sequencing identifies causes of rare diseases in 24% of previously undiagnosed patients

Researchers from Surgut State University, working with colleagues in St. Petersburg, applied whole-exome sequencing to patients whose rare diseases remained undiagnosed after conventional clinical evaluation.

The study focused on individuals with a suspected hereditary pathology for which standard diagnostic approaches had not yielded an answer.

Whole-exome sequencing examines the protein-coding regions of the genome, where the majority of known disease-causing variants reside.

The analysis identified a genetic cause in approximately 24% of the patients tested, providing a molecular diagnosis where none existed before.

The authors suggest that incorporating this method into routine practice could change how rare diseases are diagnosed across the Khanty-Mansi Autonomous Okrug and potentially throughout Russia.

The findings highlight the diagnostic yield of exome sequencing in a real-world clinical cohort after traditional workups have been exhausted.

Limitations include the study's regional scope and the fact that a majority of patients still did not receive a definitive genetic diagnosis, indicating the need for further research and broader genomic approaches.

The work demonstrates the practical value of moving from hypothesis-driven gene panels to unbiased exome-wide analysis in difficult diagnostic cases.