Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit
Genetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/9/7/2220 |
| _version_ | 1797562513326342144 |
|---|---|
| author | Robert Śmigiel Mateusz Biela Krzysztof Szmyd Michal Błoch Elżbieta Szmida Paweł Skiba Anna Walczak Piotr Gasperowicz Joanna Kosińska Małgorzata Rydzanicz Piotr Stawiński Anna Biernacka Marzena Zielińska Waldemar Gołębiowski Agnieszka Jalowska Grażyna Ohia Bożena Głowska Wojciech Walas Barbara Królak-Olejnik Paweł Krajewski Jolanta Sykut-Cegielska Maria M. Sąsiadek Rafał Płoski |
| author_facet | Robert Śmigiel Mateusz Biela Krzysztof Szmyd Michal Błoch Elżbieta Szmida Paweł Skiba Anna Walczak Piotr Gasperowicz Joanna Kosińska Małgorzata Rydzanicz Piotr Stawiński Anna Biernacka Marzena Zielińska Waldemar Gołębiowski Agnieszka Jalowska Grażyna Ohia Bożena Głowska Wojciech Walas Barbara Królak-Olejnik Paweł Krajewski Jolanta Sykut-Cegielska Maria M. Sąsiadek Rafał Płoski |
| author_sort | Robert Śmigiel |
| collection | DOAJ |
| description | Genetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing (R-WES) can be successfully performed. R-WES (singletons) was performed in 18 unrelated infants with a severe and/or progressing disease with the suspicion of genetic origin hospitalized in an Intensive Care Unit (ICU). Blood samples were also collected from the parents. The results from the R-WES were available after 5–14 days. A conclusive genetic diagnosis was obtained in 13 children, corresponding to an overall diagnostic yield of 72.2%. For nine patients, R-WES was used as a first-tier test. Eight patients were diagnosed with inborn errors of metabolism, mainly mitochondrial diseases. In two patients, the disease was possibly caused by variants in genes which so far have not been associated with human disease (<i>NARS1</i> and <i>DCAF5</i>). R-WES proved to be an effective diagnostic tool for critically ill infants in ICUs suspected of having a genetic disorder. It also should be considered as a first-tier test after precise clinical description. The quickly obtained diagnosis impacts patient’s medical management, and families can receive genetic counseling. |
| first_indexed | 2024-03-10T18:30:17Z |
| format | Article |
| id | doaj.art-1c631c393a9549f485568ceabd4af306 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T18:30:17Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-1c631c393a9549f485568ceabd4af3062023-11-20T06:38:27ZengMDPI AGJournal of Clinical Medicine2077-03832020-07-0197222010.3390/jcm9072220Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care UnitRobert Śmigiel0Mateusz Biela1Krzysztof Szmyd2Michal Błoch3Elżbieta Szmida4Paweł Skiba5Anna Walczak6Piotr Gasperowicz7Joanna Kosińska8Małgorzata Rydzanicz9Piotr Stawiński10Anna Biernacka11Marzena Zielińska12Waldemar Gołębiowski13Agnieszka Jalowska14Grażyna Ohia15Bożena Głowska16Wojciech Walas17Barbara Królak-Olejnik18Paweł Krajewski19Jolanta Sykut-Cegielska20Maria M. Sąsiadek21Rafał Płoski22Department of Pediatrics, Division Propaedeutic of Pediatrics and Rare Disorders, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Pediatrics, Division Propaedeutic of Pediatrics and Rare Disorders, Wroclaw Medical University, 50-368 Wroclaw, PolandLower Silesia Children’s Hospice, 51-163 Wroclaw, PolandDepartment of Pediatrics, Division Propaedeutic of Pediatrics and Rare Disorders, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Genetics, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Genetics, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, PolandDepartment of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, PolandDepartment of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, PolandDepartment of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, PolandDepartment of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, PolandDepartment of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, PolandDepartment of Anesthesiology and Intensive Care, Wroclaw Medical University, 50-556 Wroclaw, PolandDepartment of Anesthesiology and Intensive Care, Wroclaw Medical University, 50-556 Wroclaw, PolandDepartment of Neonatology, Wroclaw Medical University, 50-556 Wroclaw, PolandDepartment of Neonatology, Provincial Specialist Hospital, 51-124 Wroclaw, PolandDepartment of Anesthesiology and Intensive Care Unit for Newborns and Children, Provincial Specialist Hospital, 51-149 Wroclaw, PolandPediatric and Neonatal Intensive Care Unit, University Hospital, 45-401 Opole, PolandDepartment of Neonatology, Wroclaw Medical University, 50-556 Wroclaw, PolandDepartment of Forensic Medicine, Warsaw Medical University, 02-007 Warsaw, PolandDepartment of Inborn Errors of Metabolism and Pediatrics, Institute of Mother and Child, 01-211 Warsaw, PolandDepartment of Genetics, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, PolandGenetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing (R-WES) can be successfully performed. R-WES (singletons) was performed in 18 unrelated infants with a severe and/or progressing disease with the suspicion of genetic origin hospitalized in an Intensive Care Unit (ICU). Blood samples were also collected from the parents. The results from the R-WES were available after 5–14 days. A conclusive genetic diagnosis was obtained in 13 children, corresponding to an overall diagnostic yield of 72.2%. For nine patients, R-WES was used as a first-tier test. Eight patients were diagnosed with inborn errors of metabolism, mainly mitochondrial diseases. In two patients, the disease was possibly caused by variants in genes which so far have not been associated with human disease (<i>NARS1</i> and <i>DCAF5</i>). R-WES proved to be an effective diagnostic tool for critically ill infants in ICUs suspected of having a genetic disorder. It also should be considered as a first-tier test after precise clinical description. The quickly obtained diagnosis impacts patient’s medical management, and families can receive genetic counseling.https://www.mdpi.com/2077-0383/9/7/2220WESpediatric intensive care unitgenetic disordersNGSnovel diseasesfirst-tier tests |
| spellingShingle | Robert Śmigiel Mateusz Biela Krzysztof Szmyd Michal Błoch Elżbieta Szmida Paweł Skiba Anna Walczak Piotr Gasperowicz Joanna Kosińska Małgorzata Rydzanicz Piotr Stawiński Anna Biernacka Marzena Zielińska Waldemar Gołębiowski Agnieszka Jalowska Grażyna Ohia Bożena Głowska Wojciech Walas Barbara Królak-Olejnik Paweł Krajewski Jolanta Sykut-Cegielska Maria M. Sąsiadek Rafał Płoski Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit Journal of Clinical Medicine WES pediatric intensive care unit genetic disorders NGS novel diseases first-tier tests |
| title | Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit |
| title_full | Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit |
| title_fullStr | Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit |
| title_full_unstemmed | Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit |
| title_short | Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit |
| title_sort | rapid whole exome sequencing as a diagnostic tool in a neonatal pediatric intensive care unit |
| topic | WES pediatric intensive care unit genetic disorders NGS novel diseases first-tier tests |
| url | https://www.mdpi.com/2077-0383/9/7/2220 |
| work_keys_str_mv | AT robertsmigiel rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT mateuszbiela rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT krzysztofszmyd rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT michalbłoch rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT elzbietaszmida rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT pawełskiba rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT annawalczak rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT piotrgasperowicz rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT joannakosinska rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT małgorzatarydzanicz rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT piotrstawinski rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT annabiernacka rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT marzenazielinska rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT waldemargołebiowski rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT agnieszkajalowska rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT grazynaohia rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT bozenagłowska rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT wojciechwalas rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT barbarakrolakolejnik rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT pawełkrajewski rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT jolantasykutcegielska rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT mariamsasiadek rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit AT rafałpłoski rapidwholeexomesequencingasadiagnostictoolinaneonatalpediatricintensivecareunit |