Nina Pereza, Sanja Dević Pavlić, Tea Mladenić, Željka Hrupački, Dorotea Vukelić Drašković, Luca Lovrečić, Aleš Maver, Jadranka Vraneković, Iva Bilić Čače, Igor Prpić, Ivona Butorac Ahel, Vladimira Vuletić, Koraljka Benko, Tea Čaljkušić Mance, Marko Klarić, Nada Starčević Čizmarević, Ivana Babić Božović, Goran Hauser, Alen Ružić, Saša Ostojić, Borut Peterlin
The resulting dataset includes standardised gene identifiers, disease annotations, mode of inheritance, and literature support, enabling seamless integration into bioinformatic pipelines. We benchmarked 15 case studies spanning immunology, neurology, and additional disease areas. Under the recommended usage, in which the union of returned panels is considered, the causal gene was recovered in every case. Across all returned panels, the causal gene was present in 85.6% of panels. For manual interface interpretation, the causal gene was present in the user-selected best-fit panel(s) in all 15 benchmarked cases.
OBJECTIVE: This study aimed to assess the diagnostic yield, clinical indications, and utility of next-generation sequencing (NGS) testing since its implementation through collaboration between the University of Rijeka Faculty of Medicine and the Clinical Hospital Centre Rijeka.
MATERIALS AND METHODS: This retrospective study included patients referred between 2018 and 2023 from the Clinical Hospital Centre Rijeka to the University of Rijeka Faculty of Medicine for genetic testing, primarily using exome sequencing.
RESULTS: Between April 2018 and December 2023, 412 patients were referred for exome sequencing, of whom 353 (85.7%) underwent diagnostic genetic testing. A notable increase in tests ordered was observed over time. Patients were most frequently referred from Pediatrics (55.0%), Neurology (29.5%), Cardiology (7.4%), Ophthalmology (3.4%), and others (4.7%). A diagnosis was confirmed in 103/353 patients, corresponding to an overall diagnostic yield of 29.2%, and an adjusted diagnostic yield of 27.2% after collapsing related individuals into single family units. In these confirmed cases, 83 distinct disorders involving 71 unique genes were identified, with most patients showing heterozygous variants and several recurrent disorders and genes. Variants of uncertain significance were reported in 35/353 (9.9%) patients.
CONCLUSION: The 27.2% diagnostic yield demonstrates effective integration of NGS into tertiary clinical practice. The recent introduction of medical genetics specialization is expected to further improve referral quality, variant interpretation, and overall diagnostic outcomes.