De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms

Objective: The DYNC1H1 gene is related to a variety of diseases, including spinal muscular atrophy with lower extremity–predominant 1, Charcot–Marie–Tooth disease type 2O, and mental retardation, autosomal dominant13 (MRD13). Some patients with DYNC1H1 variant also had epilepsy. This study aimed to...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Haipo Yang, Pan Gong, Xianru Jiao, Yue Niu, Qiujun Zhou, Yuehua Zhang, Zhixian Yang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	infantile spasms epilepsy malformations of cortical development DYNC1H1 gene intellectual disability Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/36e7ed4af9a74eb5b284249ce0de657d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:36e7ed4af9a74eb5b284249ce0de657d
record_format	dspace
spelling	oai:doaj.org-article:36e7ed4af9a74eb5b284249ce0de657d2021-11-05T15:17:38ZDe Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms1664-229510.3389/fneur.2021.733178https://doaj.org/article/36e7ed4af9a74eb5b284249ce0de657d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.733178/fullhttps://doaj.org/toc/1664-2295Objective: The DYNC1H1 gene is related to a variety of diseases, including spinal muscular atrophy with lower extremity–predominant 1, Charcot–Marie–Tooth disease type 2O, and mental retardation, autosomal dominant13 (MRD13). Some patients with DYNC1H1 variant also had epilepsy. This study aimed to detect DYNC1H1 variants in Chinese patients with infantile spasms (ISs).Methods: We reviewed clinical information, video electroencephalogram (V-EEG), and neuroimaging of a newly identified cohort of five patients with de novo DYNC1H1gene variants.Results: Five patients with four DYNC1H1variants from four families were included. All patients had epileptic spasms (ESs), the median age at seizure onset was 7.5 months (range from 5 months to 2 years 7 months), and the interictal V-EEG results were hypsarrhythmia. Four of five patients had brain magnetic resonance imaging (MRI) abnormalities. Four de novo DYNC1H1 variants were identified, including two novel variants (p.N1117K, p.M3405L) and two reported variants (p.R1962C, p.F1093S). As for the variant site, two variants are located in the tail domain, one variant is located in the motor domain, and one variant is located in the stalk domain. All patients had tried more than five kinds of antiepileptic drugs. One patient has been controlled well by vigabatrin (VGB) for 4 years, and another patient by VGB and steroids for 1.5 years. The other three patients still had frequent ESs. All patients had severe intellectual disability and development delays.Significance: IS was one of the phenotypes of DYNC1H1 variants. Most patients had non-specific brain MRI abnormality. Two of four DYNC1H1 variants were novel, expanding the variant spectrum. The IS phenotype was related to the variant's domains of DYNC1H1 variant sites. All patients were drug-refractory and showed development delays.Haipo YangPan GongXianru JiaoYue NiuQiujun ZhouYuehua ZhangZhixian YangFrontiers Media S.A.articleinfantile spasmsepilepsymalformations of cortical developmentDYNC1H1 geneintellectual disabilityNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	infantile spasms epilepsy malformations of cortical development DYNC1H1 gene intellectual disability Neurology. Diseases of the nervous system RC346-429
spellingShingle	infantile spasms epilepsy malformations of cortical development DYNC1H1 gene intellectual disability Neurology. Diseases of the nervous system RC346-429 Haipo Yang Pan Gong Xianru Jiao Yue Niu Qiujun Zhou Yuehua Zhang Zhixian Yang De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms
description	Objective: The DYNC1H1 gene is related to a variety of diseases, including spinal muscular atrophy with lower extremity–predominant 1, Charcot–Marie–Tooth disease type 2O, and mental retardation, autosomal dominant13 (MRD13). Some patients with DYNC1H1 variant also had epilepsy. This study aimed to detect DYNC1H1 variants in Chinese patients with infantile spasms (ISs).Methods: We reviewed clinical information, video electroencephalogram (V-EEG), and neuroimaging of a newly identified cohort of five patients with de novo DYNC1H1gene variants.Results: Five patients with four DYNC1H1variants from four families were included. All patients had epileptic spasms (ESs), the median age at seizure onset was 7.5 months (range from 5 months to 2 years 7 months), and the interictal V-EEG results were hypsarrhythmia. Four of five patients had brain magnetic resonance imaging (MRI) abnormalities. Four de novo DYNC1H1 variants were identified, including two novel variants (p.N1117K, p.M3405L) and two reported variants (p.R1962C, p.F1093S). As for the variant site, two variants are located in the tail domain, one variant is located in the motor domain, and one variant is located in the stalk domain. All patients had tried more than five kinds of antiepileptic drugs. One patient has been controlled well by vigabatrin (VGB) for 4 years, and another patient by VGB and steroids for 1.5 years. The other three patients still had frequent ESs. All patients had severe intellectual disability and development delays.Significance: IS was one of the phenotypes of DYNC1H1 variants. Most patients had non-specific brain MRI abnormality. Two of four DYNC1H1 variants were novel, expanding the variant spectrum. The IS phenotype was related to the variant's domains of DYNC1H1 variant sites. All patients were drug-refractory and showed development delays.
format	article
author	Haipo Yang Pan Gong Xianru Jiao Yue Niu Qiujun Zhou Yuehua Zhang Zhixian Yang
author_facet	Haipo Yang Pan Gong Xianru Jiao Yue Niu Qiujun Zhou Yuehua Zhang Zhixian Yang
author_sort	Haipo Yang
title	De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms
title_short	De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms
title_full	De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms
title_fullStr	De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms
title_full_unstemmed	De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms
title_sort	de novo variants in the dync1h1 gene associated with infantile spasms
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/36e7ed4af9a74eb5b284249ce0de657d
work_keys_str_mv	AT haipoyang denovovariantsinthedync1h1geneassociatedwithinfantilespasms AT pangong denovovariantsinthedync1h1geneassociatedwithinfantilespasms AT xianrujiao denovovariantsinthedync1h1geneassociatedwithinfantilespasms AT yueniu denovovariantsinthedync1h1geneassociatedwithinfantilespasms AT qiujunzhou denovovariantsinthedync1h1geneassociatedwithinfantilespasms AT yuehuazhang denovovariantsinthedync1h1geneassociatedwithinfantilespasms AT zhixianyang denovovariantsinthedync1h1geneassociatedwithinfantilespasms
_version_	1718444154863747072

De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms

Ejemplares similares