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Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy

Epilepsy is one of the most common neurological disorders in pediatric patients with other underlying neurological defects. Identifying the underlying etiology is crucial for better management of the disorder. We performed trio-whole exome sequencing in 221 pediatric patients with epilepsy. Probands...

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Autores principales: Jiang, Tiejia, Gao, Jia, Jiang, Lihua, Xu, Lu, Zhao, Congying, Su, Xiaojun, Shen, Yaping, Gu, Weiyue, Kong, Xiaohong, Yang, Ying, Gao, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417468/
https://www.ncbi.nlm.nih.gov/pubmed/34489640
http://dx.doi.org/10.3389/fnmol.2021.699574
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author Jiang, Tiejia
Gao, Jia
Jiang, Lihua
Xu, Lu
Zhao, Congying
Su, Xiaojun
Shen, Yaping
Gu, Weiyue
Kong, Xiaohong
Yang, Ying
Gao, Feng
author_facet Jiang, Tiejia
Gao, Jia
Jiang, Lihua
Xu, Lu
Zhao, Congying
Su, Xiaojun
Shen, Yaping
Gu, Weiyue
Kong, Xiaohong
Yang, Ying
Gao, Feng
author_sort Jiang, Tiejia
collection PubMed
description Epilepsy is one of the most common neurological disorders in pediatric patients with other underlying neurological defects. Identifying the underlying etiology is crucial for better management of the disorder. We performed trio-whole exome sequencing in 221 pediatric patients with epilepsy. Probands were divided into seizures with developmental delay/intellectual disability (DD/ID) and seizures without DD/ID groups. Pathogenic (P) or likely pathogenic (LP) variants were identified in 71/110 (64.5%) patients in the seizures with DD/ID group and 21/111 (18.9%) patients in the seizures without DD/ID group (P < 0.001). Eighty-seven distinct P/LP single nucleotide variants (SNVs)/insertion deletions (Indels) were detected, with 55.2% (48/87) of them being novel. All aneuploidy and P/LP copy number variants (CNVs) larger than 100 Kb were identifiable by both whole-exome sequencing and copy number variation sequencing (CNVseq) in 123 of individuals (41 pedigrees). Ten of P/LP CNVs in nine patients and one aneuploidy variant in one patient (Patient #56, #47, XXY) were identified by CNVseq. Herein, we identified seven genes (NCL, SEPHS2, PA2G4, SLC35G2, MYO1C, GPR158, and POU3F1) with de novo variants but unknown pathogenicity that were not previously associated with epilepsy. Potential effective treatment options were available for 32 patients with a P/LP variant, based on the molecular diagnosis. Genetic testing may help identify the molecular etiology of early onset epilepsy and DD/ID and further aid to choose the appropriate treatment strategy for patients.
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spelling pubmed-84174682021-09-05 Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy Jiang, Tiejia Gao, Jia Jiang, Lihua Xu, Lu Zhao, Congying Su, Xiaojun Shen, Yaping Gu, Weiyue Kong, Xiaohong Yang, Ying Gao, Feng Front Mol Neurosci Neuroscience Epilepsy is one of the most common neurological disorders in pediatric patients with other underlying neurological defects. Identifying the underlying etiology is crucial for better management of the disorder. We performed trio-whole exome sequencing in 221 pediatric patients with epilepsy. Probands were divided into seizures with developmental delay/intellectual disability (DD/ID) and seizures without DD/ID groups. Pathogenic (P) or likely pathogenic (LP) variants were identified in 71/110 (64.5%) patients in the seizures with DD/ID group and 21/111 (18.9%) patients in the seizures without DD/ID group (P < 0.001). Eighty-seven distinct P/LP single nucleotide variants (SNVs)/insertion deletions (Indels) were detected, with 55.2% (48/87) of them being novel. All aneuploidy and P/LP copy number variants (CNVs) larger than 100 Kb were identifiable by both whole-exome sequencing and copy number variation sequencing (CNVseq) in 123 of individuals (41 pedigrees). Ten of P/LP CNVs in nine patients and one aneuploidy variant in one patient (Patient #56, #47, XXY) were identified by CNVseq. Herein, we identified seven genes (NCL, SEPHS2, PA2G4, SLC35G2, MYO1C, GPR158, and POU3F1) with de novo variants but unknown pathogenicity that were not previously associated with epilepsy. Potential effective treatment options were available for 32 patients with a P/LP variant, based on the molecular diagnosis. Genetic testing may help identify the molecular etiology of early onset epilepsy and DD/ID and further aid to choose the appropriate treatment strategy for patients. Frontiers Media S.A. 2021-08-19 /pmc/articles/PMC8417468/ /pubmed/34489640 http://dx.doi.org/10.3389/fnmol.2021.699574 Text en Copyright © 2021 Jiang, Gao, Jiang, Xu, Zhao, Su, Shen, Gu, Kong, Yang and Gao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Jiang, Tiejia
Gao, Jia
Jiang, Lihua
Xu, Lu
Zhao, Congying
Su, Xiaojun
Shen, Yaping
Gu, Weiyue
Kong, Xiaohong
Yang, Ying
Gao, Feng
Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy
title Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy
title_full Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy
title_fullStr Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy
title_full_unstemmed Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy
title_short Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy
title_sort application of trio-whole exome sequencing in genetic diagnosis and therapy in chinese children with epilepsy
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417468/
https://www.ncbi.nlm.nih.gov/pubmed/34489640
http://dx.doi.org/10.3389/fnmol.2021.699574
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