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Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy

Objective: The genetic aetiology of epileptic encephalopathy (EE) is growing rapidly based on next generation sequencing (NGS) results. In this single-centre study, we aimed to investigate a cohort of Chinese children with early infantile epileptic encephalopathy (EIEE). Methods: NGS was performed o...

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Autores principales: Liu, Xianyu, Shen, Qiyang, Zheng, Guo, Guo, Hu, Lu, Xiaopeng, Wang, Xiaoyu, Yang, Xiao, Cao, Zixuan, Chen, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215605/
https://www.ncbi.nlm.nih.gov/pubmed/34163418
http://dx.doi.org/10.3389/fneur.2021.633637
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author Liu, Xianyu
Shen, Qiyang
Zheng, Guo
Guo, Hu
Lu, Xiaopeng
Wang, Xiaoyu
Yang, Xiao
Cao, Zixuan
Chen, Jing
author_facet Liu, Xianyu
Shen, Qiyang
Zheng, Guo
Guo, Hu
Lu, Xiaopeng
Wang, Xiaoyu
Yang, Xiao
Cao, Zixuan
Chen, Jing
author_sort Liu, Xianyu
collection PubMed
description Objective: The genetic aetiology of epileptic encephalopathy (EE) is growing rapidly based on next generation sequencing (NGS) results. In this single-centre study, we aimed to investigate a cohort of Chinese children with early infantile epileptic encephalopathy (EIEE). Methods: NGS was performed on 50 children with unexplained EIEE. The clinical profiles of children with pathogenic variants were characterised and analysed in detail. Conservation analysis and homology modelling were performed to predict the impact of STXBP1 variant on the protein structure. Results: Pathogenic variants were identified in 17 (34%) of 50 children. Sixteen variants including STXBP1 (n = 2), CDKL5 (n = 2), PAFAH1B1, SCN1A (n = 9), SCN2A, and KCNQ2 were de novo, and one (PIGN) was a compound heterozygous variant. The phenotypes of the identified genes were broadened. PIGN phenotypic spectrum may include EIEE. The STXBP1 variants were predicted to affect protein stability. Significance: NGS is a useful diagnostic tool for EIEE and contributes to expanding the EIEE-associated genotypes. Early diagnosis may lead to precise therapeutic interventions and can improve the developmental outcome.
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spelling pubmed-82156052021-06-22 Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy Liu, Xianyu Shen, Qiyang Zheng, Guo Guo, Hu Lu, Xiaopeng Wang, Xiaoyu Yang, Xiao Cao, Zixuan Chen, Jing Front Neurol Neurology Objective: The genetic aetiology of epileptic encephalopathy (EE) is growing rapidly based on next generation sequencing (NGS) results. In this single-centre study, we aimed to investigate a cohort of Chinese children with early infantile epileptic encephalopathy (EIEE). Methods: NGS was performed on 50 children with unexplained EIEE. The clinical profiles of children with pathogenic variants were characterised and analysed in detail. Conservation analysis and homology modelling were performed to predict the impact of STXBP1 variant on the protein structure. Results: Pathogenic variants were identified in 17 (34%) of 50 children. Sixteen variants including STXBP1 (n = 2), CDKL5 (n = 2), PAFAH1B1, SCN1A (n = 9), SCN2A, and KCNQ2 were de novo, and one (PIGN) was a compound heterozygous variant. The phenotypes of the identified genes were broadened. PIGN phenotypic spectrum may include EIEE. The STXBP1 variants were predicted to affect protein stability. Significance: NGS is a useful diagnostic tool for EIEE and contributes to expanding the EIEE-associated genotypes. Early diagnosis may lead to precise therapeutic interventions and can improve the developmental outcome. Frontiers Media S.A. 2021-06-07 /pmc/articles/PMC8215605/ /pubmed/34163418 http://dx.doi.org/10.3389/fneur.2021.633637 Text en Copyright © 2021 Liu, Shen, Zheng, Guo, Lu, Wang, Yang, Cao and Chen. 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 Neurology
Liu, Xianyu
Shen, Qiyang
Zheng, Guo
Guo, Hu
Lu, Xiaopeng
Wang, Xiaoyu
Yang, Xiao
Cao, Zixuan
Chen, Jing
Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy
title Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy
title_full Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy
title_fullStr Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy
title_full_unstemmed Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy
title_short Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy
title_sort gene and phenotype expansion of unexplained early infantile epileptic encephalopathy
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215605/
https://www.ncbi.nlm.nih.gov/pubmed/34163418
http://dx.doi.org/10.3389/fneur.2021.633637
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