Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases
Abstract 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-la...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-79872-4 |
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| author | Katerina Slaba Petra Pokorna Robin Jugas Hana Palova Dagmar Prochazkova Stefania Aulicka Klara Spanelova Pavlina Danhofer Ondrej Horak Jana Tuckova Petra Kleiblova Renata Gaillyova Matej Hrunka Martin Jouza Blanka Pinkova Jan Papez Petra Konecna Jana Zidkova Petr Stourac Jaroslav Sterba Regina Demlova Eva Demlova Petr Jabandziev Ondrej Slaby |
| author_facet | Katerina Slaba Petra Pokorna Robin Jugas Hana Palova Dagmar Prochazkova Stefania Aulicka Klara Spanelova Pavlina Danhofer Ondrej Horak Jana Tuckova Petra Kleiblova Renata Gaillyova Matej Hrunka Martin Jouza Blanka Pinkova Jan Papez Petra Konecna Jana Zidkova Petr Stourac Jaroslav Sterba Regina Demlova Eva Demlova Petr Jabandziev Ondrej Slaby |
| author_sort | Katerina Slaba |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-5632c7178ab1493c9496854f9b2ecf9d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-5632c7178ab1493c9496854f9b2ecf9d2024-11-24T12:19:53ZengNature PortfolioScientific Reports2045-23222024-11-0114111110.1038/s41598-024-79872-4Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseasesKaterina Slaba0Petra Pokorna1Robin Jugas2Hana Palova3Dagmar Prochazkova4Stefania Aulicka5Klara Spanelova6Pavlina Danhofer7Ondrej Horak8Jana Tuckova9Petra Kleiblova10Renata Gaillyova11Matej Hrunka12Martin Jouza13Blanka Pinkova14Jan Papez15Petra Konecna16Jana Zidkova17Petr Stourac18Jaroslav Sterba19Regina Demlova20Eva Demlova21Petr Jabandziev22Ondrej Slaby23Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk UniversityCentral European Institute of Technology, Masaryk UniversityCentral European Institute of Technology, Masaryk UniversityCentral European Institute of Technology, Masaryk UniversityDepartment of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk UniversityDepartment of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk UniversityDepartment of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk UniversityDepartment of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk UniversityDepartment of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk UniversityDepartment of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk UniversityInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in PragueDepartment of Medical Genetics and Genomics, University Hospital Brno, Faculty of Medicine, Masaryk University BrnoDepartment of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk UniversityDepartment of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk UniversityDepartment of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk UniversityDepartment of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk UniversityDepartment of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk UniversityCentre of Molecular Biology and Genetics, Department of Hematology, Oncology and Internal Medicine, Masaryk University and University Hospital BrnoDepartment of Pediatric Anesthesiology and Intensive Care Medicine, University Hospital Brno and Faculty of Medicine, Masaryk UniversityDepartment of Pediatric Oncology, Faculty of Medicine, University Hospital Brno, Masaryk UniversityDepartment of Pharmacology/CZECRIN, Masaryk University Faculty of MedicineDepartment of Pharmacology/CZECRIN, Masaryk University Faculty of MedicineDepartment of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk UniversityCentral European Institute of Technology, Masaryk UniversityAbstract 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.https://doi.org/10.1038/s41598-024-79872-4Rare genetic diseasesUndiagnosed patientsWhole-exome sequencing |
| spellingShingle | Katerina Slaba Petra Pokorna Robin Jugas Hana Palova Dagmar Prochazkova Stefania Aulicka Klara Spanelova Pavlina Danhofer Ondrej Horak Jana Tuckova Petra Kleiblova Renata Gaillyova Matej Hrunka Martin Jouza Blanka Pinkova Jan Papez Petra Konecna Jana Zidkova Petr Stourac Jaroslav Sterba Regina Demlova Eva Demlova Petr Jabandziev Ondrej Slaby Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases Scientific Reports Rare genetic diseases Undiagnosed patients Whole-exome sequencing |
| title | Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases |
| title_full | Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases |
| title_fullStr | Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases |
| title_full_unstemmed | Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases |
| title_short | Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases |
| title_sort | diagnostic efficacy and clinical utility of whole exome sequencing in czech pediatric patients with rare and undiagnosed diseases |
| topic | Rare genetic diseases Undiagnosed patients Whole-exome sequencing |
| url | https://doi.org/10.1038/s41598-024-79872-4 |
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