Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies

Abstract Epileptic encephalopathies (EE) are a group of severe childhood epilepsy disorders characterized by intractable seizures, cognitive impairment and neurological deficits. Recent whole-exome sequencing (WES) studies have implicated significant contribution of de novo mutations to EE. In this...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhongdong Lin, Zhenwei Liu, Xiucui Li, Feng Li, Ying Hu, Bingyu Chen, Zhen Wang, Yong Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a1aa4273b54243acad864b1e15474333
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a1aa4273b54243acad864b1e15474333
record_format	dspace
spelling	oai:doaj.org-article:a1aa4273b54243acad864b1e154743332021-12-02T11:41:12ZWhole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies10.1038/s41598-017-00208-62045-2322https://doaj.org/article/a1aa4273b54243acad864b1e154743332017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00208-6https://doaj.org/toc/2045-2322Abstract Epileptic encephalopathies (EE) are a group of severe childhood epilepsy disorders characterized by intractable seizures, cognitive impairment and neurological deficits. Recent whole-exome sequencing (WES) studies have implicated significant contribution of de novo mutations to EE. In this study, we utilized WES for identifying causal de novo mutations in 4 parent-offspring trios affected by West syndrome. As a result, we found two deleterious de novo mutations in DYNC1H1 and RTP1 in two trios. Expression profile analysis showed that DYNC1H1 and RTP1 are expressed in almost all brain regions and developmental stages. Interestingly, co-expression and genetic interaction network analyses suggested that DYNC1H1 and RTP1 are tightly associated with known epilepsy genes. Furthermore, we observed that the de novo mutations of DYNC1H1 were identified in several different neuropsychiatric disorders including EE, autism spectrum disorders and intellectual disabilities by previous studies, and these mutations primarily occurred in the functional domain of the protein. Taken together, these results demonstrate DYNC1H1 as a strong candidate and RTP1 as a potential candidate on the onset of EE. In addition, this work also proves WES as a powerful tool for the molecular genetic dissection of children affected by sporadic EE.Zhongdong LinZhenwei LiuXiucui LiFeng LiYing HuBingyu ChenZhen WangYong LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhongdong Lin Zhenwei Liu Xiucui Li Feng Li Ying Hu Bingyu Chen Zhen Wang Yong Liu Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies
description	Abstract Epileptic encephalopathies (EE) are a group of severe childhood epilepsy disorders characterized by intractable seizures, cognitive impairment and neurological deficits. Recent whole-exome sequencing (WES) studies have implicated significant contribution of de novo mutations to EE. In this study, we utilized WES for identifying causal de novo mutations in 4 parent-offspring trios affected by West syndrome. As a result, we found two deleterious de novo mutations in DYNC1H1 and RTP1 in two trios. Expression profile analysis showed that DYNC1H1 and RTP1 are expressed in almost all brain regions and developmental stages. Interestingly, co-expression and genetic interaction network analyses suggested that DYNC1H1 and RTP1 are tightly associated with known epilepsy genes. Furthermore, we observed that the de novo mutations of DYNC1H1 were identified in several different neuropsychiatric disorders including EE, autism spectrum disorders and intellectual disabilities by previous studies, and these mutations primarily occurred in the functional domain of the protein. Taken together, these results demonstrate DYNC1H1 as a strong candidate and RTP1 as a potential candidate on the onset of EE. In addition, this work also proves WES as a powerful tool for the molecular genetic dissection of children affected by sporadic EE.
format	article
author	Zhongdong Lin Zhenwei Liu Xiucui Li Feng Li Ying Hu Bingyu Chen Zhen Wang Yong Liu
author_facet	Zhongdong Lin Zhenwei Liu Xiucui Li Feng Li Ying Hu Bingyu Chen Zhen Wang Yong Liu
author_sort	Zhongdong Lin
title	Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies
title_short	Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies
title_full	Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies
title_fullStr	Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies
title_full_unstemmed	Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies
title_sort	whole-exome sequencing identifies a novel de novo mutation in dync1h1 in epileptic encephalopathies
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a1aa4273b54243acad864b1e15474333
work_keys_str_mv	AT zhongdonglin wholeexomesequencingidentifiesanoveldenovomutationindync1h1inepilepticencephalopathies AT zhenweiliu wholeexomesequencingidentifiesanoveldenovomutationindync1h1inepilepticencephalopathies AT xiucuili wholeexomesequencingidentifiesanoveldenovomutationindync1h1inepilepticencephalopathies AT fengli wholeexomesequencingidentifiesanoveldenovomutationindync1h1inepilepticencephalopathies AT yinghu wholeexomesequencingidentifiesanoveldenovomutationindync1h1inepilepticencephalopathies AT bingyuchen wholeexomesequencingidentifiesanoveldenovomutationindync1h1inepilepticencephalopathies AT zhenwang wholeexomesequencingidentifiesanoveldenovomutationindync1h1inepilepticencephalopathies AT yongliu wholeexomesequencingidentifiesanoveldenovomutationindync1h1inepilepticencephalopathies
_version_	1718395476231847936

Whole-exome sequencing identifies a novel de novo mutation in DYNC1H1 in epileptic encephalopathies

Ejemplares similares