Cargando…

Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life

BACKGROUND: Epilepsy is a heterogeneous disease with a broad phenotypic spectrum and diverse genotypes. A significant proportion of epilepsies has a genetic aetiology. In our study, a custom designed gene panel with 112 genes known to be associated with epilepsies was used. In total, one hundred and...

Descripción completa

Detalles Bibliográficos
Autores principales: Staněk, David, Laššuthová, Petra, Štěrbová, Katalin, Vlčková, Markéta, Neupauerová, Jana, Krůtová, Marcela, Seeman, Pavel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932755/
https://www.ncbi.nlm.nih.gov/pubmed/29720203
http://dx.doi.org/10.1186/s13023-018-0812-8
_version_ 1783319860643627008
author Staněk, David
Laššuthová, Petra
Štěrbová, Katalin
Vlčková, Markéta
Neupauerová, Jana
Krůtová, Marcela
Seeman, Pavel
author_facet Staněk, David
Laššuthová, Petra
Štěrbová, Katalin
Vlčková, Markéta
Neupauerová, Jana
Krůtová, Marcela
Seeman, Pavel
author_sort Staněk, David
collection PubMed
description BACKGROUND: Epilepsy is a heterogeneous disease with a broad phenotypic spectrum and diverse genotypes. A significant proportion of epilepsies has a genetic aetiology. In our study, a custom designed gene panel with 112 genes known to be associated with epilepsies was used. In total, one hundred and fifty-one patients were tested (86 males / 65 females). RESULTS: In our cohort, the highest probability for the identification of the cause of the disease was for patients with a seizure onset within the first four weeks of life (61.9% clarification rate) – about two times more than other groups. The level of statistical significance was determined using a chi-square analysis. From 112 genes included in the panel, suspicious and rare variants were found in 53 genes (47.3%). Among the 151 probands included in the study we identified pathogenic variants in 39 patients (25.8%), likely pathogenic variants in three patients (2%), variants of uncertain significance in 40 patients (26.5%) and likely benign variants in 69 patients (45.7%). CONCLUSION: Our report shows the utility of diagnostic genetic testing of severe childhood epilepsies in a large cohort of patients with a diagnostic rate of 25.8%. A gene panel can be considered as a method of choice for the detection of pathogenic variants within patients with unknown origin of early onset severe epilepsy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-018-0812-8) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5932755
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-59327552018-05-09 Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life Staněk, David Laššuthová, Petra Štěrbová, Katalin Vlčková, Markéta Neupauerová, Jana Krůtová, Marcela Seeman, Pavel Orphanet J Rare Dis Research BACKGROUND: Epilepsy is a heterogeneous disease with a broad phenotypic spectrum and diverse genotypes. A significant proportion of epilepsies has a genetic aetiology. In our study, a custom designed gene panel with 112 genes known to be associated with epilepsies was used. In total, one hundred and fifty-one patients were tested (86 males / 65 females). RESULTS: In our cohort, the highest probability for the identification of the cause of the disease was for patients with a seizure onset within the first four weeks of life (61.9% clarification rate) – about two times more than other groups. The level of statistical significance was determined using a chi-square analysis. From 112 genes included in the panel, suspicious and rare variants were found in 53 genes (47.3%). Among the 151 probands included in the study we identified pathogenic variants in 39 patients (25.8%), likely pathogenic variants in three patients (2%), variants of uncertain significance in 40 patients (26.5%) and likely benign variants in 69 patients (45.7%). CONCLUSION: Our report shows the utility of diagnostic genetic testing of severe childhood epilepsies in a large cohort of patients with a diagnostic rate of 25.8%. A gene panel can be considered as a method of choice for the detection of pathogenic variants within patients with unknown origin of early onset severe epilepsy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-018-0812-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-02 /pmc/articles/PMC5932755/ /pubmed/29720203 http://dx.doi.org/10.1186/s13023-018-0812-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Staněk, David
Laššuthová, Petra
Štěrbová, Katalin
Vlčková, Markéta
Neupauerová, Jana
Krůtová, Marcela
Seeman, Pavel
Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life
title Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life
title_full Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life
title_fullStr Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life
title_full_unstemmed Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life
title_short Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life
title_sort detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932755/
https://www.ncbi.nlm.nih.gov/pubmed/29720203
http://dx.doi.org/10.1186/s13023-018-0812-8
work_keys_str_mv AT stanekdavid detectionrateofcausalvariantsinseverechildhoodepilepsyishighestinpatientswithseizureonsetwithinthefirstfourweeksoflife
AT lassuthovapetra detectionrateofcausalvariantsinseverechildhoodepilepsyishighestinpatientswithseizureonsetwithinthefirstfourweeksoflife
AT sterbovakatalin detectionrateofcausalvariantsinseverechildhoodepilepsyishighestinpatientswithseizureonsetwithinthefirstfourweeksoflife
AT vlckovamarketa detectionrateofcausalvariantsinseverechildhoodepilepsyishighestinpatientswithseizureonsetwithinthefirstfourweeksoflife
AT neupauerovajana detectionrateofcausalvariantsinseverechildhoodepilepsyishighestinpatientswithseizureonsetwithinthefirstfourweeksoflife
AT krutovamarcela detectionrateofcausalvariantsinseverechildhoodepilepsyishighestinpatientswithseizureonsetwithinthefirstfourweeksoflife
AT seemanpavel detectionrateofcausalvariantsinseverechildhoodepilepsyishighestinpatientswithseizureonsetwithinthefirstfourweeksoflife