-
Something wrong with this record ?
Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases
K. Slaba, P. Pokorna, R. Jugas, H. Palova, D. Prochazkova, S. Aulicka, K. Spanelova, P. Danhofer, O. Horak, J. Tuckova, P. Kleiblova, R. Gaillyova, M. Hrunka, M. Jouza, B. Pinkova, J. Papez, P. Konecna, J. Zidkova, P. Stourac, J. Sterba, R....
Language English Country England, Great Britain
Document type Journal Article
Grant support
65269705
Ministry of Health, Czech Republic, Conceptual Development of Research Organization
101059788
European Union’s Horizon Europe Coordination and Support Action
NLK
Directory of Open Access Journals
from 2011
Free Medical Journals
from 2011
Nature Open Access
from 2011-12-01
PubMed Central
from 2011
Europe PubMed Central
from 2011
ProQuest Central
from 2011-01-01
Open Access Digital Library
from 2011-01-01
Open Access Digital Library
from 2011-01-01
Health & Medicine (ProQuest)
from 2011-01-01
ROAD: Directory of Open Access Scholarly Resources
from 2011
Springer Nature OA/Free Journals
from 2011-12-01
- MeSH
- Child MeSH
- Genetic Testing methods MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Undiagnosed Diseases * genetics diagnosis epidemiology MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Prospective Studies MeSH
- Exome Sequencing * methods MeSH
- Rare Diseases * genetics diagnosis MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
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.
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
Department of Pharmacology CZECRIN Masaryk University Faculty of Medicine Brno Czech Republic
Department of Simulation Medicine Faculty of Medicine Masaryk University Brno Czech Republic
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc25003427
- 003
- CZ-PrNML
- 005
- 20250206104334.0
- 007
- ta
- 008
- 250121s2024 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1038/s41598-024-79872-4 $2 doi
- 035 __
- $a (PubMed)39567597
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Slaba, Katerina $u Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic. slaba.katerina@fnbrno.cz
- 245 10
- $a Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases / $c K. Slaba, P. Pokorna, R. Jugas, H. Palova, D. Prochazkova, S. Aulicka, K. Spanelova, P. Danhofer, O. Horak, J. Tuckova, P. Kleiblova, R. Gaillyova, M. Hrunka, M. Jouza, B. Pinkova, J. Papez, P. Konecna, J. Zidkova, P. Stourac, J. Sterba, R. Demlova, E. Demlova, P. Jabandziev, O. Slaby
- 520 9_
- $a 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.
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a dítě $7 D002648
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 12
- $a sekvenování exomu $x metody $7 D000073359
- 650 _2
- $a předškolní dítě $7 D002675
- 650 12
- $a vzácné nemoci $x genetika $x diagnóza $7 D035583
- 650 _2
- $a kojenec $7 D007223
- 650 _2
- $a mladiství $7 D000293
- 650 12
- $a nediagnostikované nemoci $x genetika $x diagnóza $x epidemiologie $7 D000080842
- 650 _2
- $a genetické testování $x metody $7 D005820
- 650 _2
- $a novorozenec $7 D007231
- 650 _2
- $a prospektivní studie $7 D011446
- 651 _2
- $a Česká republika $7 D018153
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Pokorna, Petra $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic
- 700 1_
- $a Jugas, Robin $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic
- 700 1_
- $a Palova, Hana $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Prochazkova, Dagmar $u Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic
- 700 1_
- $a Aulicka, Stefania $u Department of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Spanelova, Klara $u Department of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Danhofer, Pavlina $u Department of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Horak, Ondrej $u Department of Pediatric Neurology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Tuckova, Jana $u Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic
- 700 1_
- $a Kleiblova, Petra $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic $u Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Gaillyova, Renata $u Department of Medical Genetics and Genomics, University Hospital Brno, Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic
- 700 1_
- $a Hrunka, Matej $u Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic
- 700 1_
- $a Jouza, Martin $u Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic
- 700 1_
- $a Pinkova, Blanka $u Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic
- 700 1_
- $a Papez, Jan $u Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic
- 700 1_
- $a Konecna, Petra $u Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic
- 700 1_
- $a Zidkova, Jana $u Centre of Molecular Biology and Genetics, Department of Hematology, Oncology and Internal Medicine, Masaryk University and University Hospital Brno, Brno, Czech Republic
- 700 1_
- $a Stourac, Petr $u Department of Pediatric Anesthesiology and Intensive Care Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic $u Department of Simulation Medicine, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Sterba, Jaroslav $u Department of Pediatric Oncology, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Demlova, Regina $u Department of Pharmacology/CZECRIN, Masaryk University Faculty of Medicine, Brno, Czech Republic
- 700 1_
- $a Demlova, Eva $u Department of Pharmacology/CZECRIN, Masaryk University Faculty of Medicine, Brno, Czech Republic
- 700 1_
- $a Jabandziev, Petr $u Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Slaby, Ondrej $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic. oslaby@med.muni.cz $u Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic. oslaby@med.muni.cz $u Center of Precision Medicine, Department of Pathology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic. oslaby@med.muni.cz
- 773 0_
- $w MED00182195 $t Scientific reports $x 2045-2322 $g Roč. 14, č. 1 (2024), s. 28780
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/39567597 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20250121 $b ABA008
- 991 __
- $a 20250206104329 $b ABA008
- 999 __
- $a ok $b bmc $g 2263292 $s 1239434
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 14 $c 1 $d 28780 $e 20241120 $i 2045-2322 $m Scientific reports $n Sci Rep $x MED00182195
- GRA __
- $a 65269705 $p Ministry of Health, Czech Republic, Conceptual Development of Research Organization
- GRA __
- $a 101059788 $p European Union’s Horizon Europe Coordination and Support Action
- LZP __
- $a Pubmed-20250121
