Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases.

Autor: Slaba K; Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic. slaba.katerina@fnbrno.cz., Pokorna P; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.; Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic., Jugas R; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.; Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic., Palova H; Central European Institute of Technology, Masaryk University, Brno, Czech Republic., Prochazkova D; Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic., Aulicka S; Department of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic., Spanelova K; Department of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic., Danhofer P; Department of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic., Horak O; Department of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic., Tuckova J; Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic., Kleiblova P; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic., Gaillyova R; Department of Medical Genetics and Genomics, University Hospital Brno, Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic., Hrunka M; Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic., Jouza M; Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic., Pinkova B; Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic., Papez J; Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic., Konecna P; Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic., Zidkova J; Centre of Molecular Biology and Genetics, Department of Hematology, Oncology and Internal Medicine, Masaryk University and University Hospital Brno, Brno, Czech Republic., Stourac P; Department of Pediatric Anesthesiology and Intensive Care Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.; Department of Simulation Medicine, Faculty of Medicine, Masaryk University, Brno, Czech Republic., Sterba J; Department of Pediatric Oncology, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic., Demlova R; Department of Pharmacology/CZECRIN, Masaryk University Faculty of Medicine, Brno, Czech Republic., Demlova E; Department of Pharmacology/CZECRIN, Masaryk University Faculty of Medicine, Brno, Czech Republic., Jabandziev P; Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic.; Central European Institute of Technology, Masaryk University, Brno, Czech Republic., Slaby O; Central European Institute of Technology, Masaryk University, Brno, Czech Republic. oslaby@med.muni.cz.; Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic. oslaby@med.muni.cz.; Center of Precision Medicine, Department of Pathology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic. oslaby@med.muni.cz.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 20; Vol. 14 (1), pp. 28780. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1038/s41598-024-79872-4
Abstrakt: In the last decade, undiagnosed disease programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases. In our single-center study, we have launched a pilot program for pediatric patients with undiagnosed diseases in the second-largest university hospital in the Czech Republic. This study was prospectively conducted at the Department of Pediatrics at University Hospital Brno between 2020 and 2023. A total of 58 Czech patients with undiagnosed diseases were enrolled in the study. All children underwent singleton WES with targeted phenotype-driven analysis. We identified 28 variants, including 11 pathogenic, 13 likely pathogenic, and 4 VUS according to ACMG guidelines, as diagnostic of genetic diseases in 25 patients, resulting in an overall diagnostic yield of 43%. Eleven variants were novel and had not been previously reported in any public database. The overall clinical utility (actionability) enabling at least one type of change in the medical care of the patient was 76%, whereas the average number of clinical implications to individual patient care was two. Singleton WES facilitated the diagnostic process in the Czech undiagnosed pediatric population. We believe it is an effective approach to enable appropriate counseling, surveillance, and personalized clinical management.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The study was approved by the University Hospital Brno Ethics Committee (approvals no. 31-270420 and 12-071222), and informed consent was obtained from all participants or their legal representatives. The participants’ legal representatives provided written informed consent to participate in this study. Consent for publication: Informed consent to publish de-identified data was received from all participants and/or participants’ legal representatives who participated in the study.
(© 2024. The Author(s).)
Databáze: MEDLINE
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