Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease involving the upper and lower motor neurons of the spinal cord, brainstem, and cerebral cortex. At least 30 genes have been implicated in familial ALS (fALS) and sporadic ALS (sALS). Kaneb et al. (2015) first carrie...

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Main Authors: Yanran Li, Bo Sun, Zhanjun Wang, Zhengqing He, Fei Yang, Hongfen Wang, Fang Cui, Zhaohui Chen, Li Ling, Chaodong Wang, Xusheng Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2021.595775/full
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spelling doaj-9e6ab379c02043639c75583440d2a9422021-05-05T04:27:33ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-05-011510.3389/fnins.2021.595775595775Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis PatientsYanran Li0Bo Sun1Zhanjun Wang2Zhengqing He3Fei Yang4Hongfen Wang5Fang Cui6Zhaohui Chen7Li Ling8Chaodong Wang9Xusheng Huang10Neurological Department of the First Medical Center, Chinese PLA General Hospital, Beijing, ChinaGeriatric Neurological Department of the Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaNeurological Department of the First Medical Center, Chinese PLA General Hospital, Beijing, ChinaNeurological Department of the First Medical Center, Chinese PLA General Hospital, Beijing, ChinaNeurological Department of the First Medical Center, Chinese PLA General Hospital, Beijing, ChinaNeurological Department of the First Medical Center, Chinese PLA General Hospital, Beijing, ChinaNeurological Department of the First Medical Center, Chinese PLA General Hospital, Beijing, ChinaNeurological Department of the First Medical Center, Chinese PLA General Hospital, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaNeurological Department of the First Medical Center, Chinese PLA General Hospital, Beijing, ChinaAmyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease involving the upper and lower motor neurons of the spinal cord, brainstem, and cerebral cortex. At least 30 genes have been implicated in familial ALS (fALS) and sporadic ALS (sALS). Kaneb et al. (2015) first carried out a large-scale sequencing study in ALS patients and identified two loss-of-function (LOF) variants in the GLE1 gene. The LOF mutation-induced disruption of RNA metabolism through the haploinsufficiency mechanism is implicated in ALS pathogenesis. A total of 628 ALS patients and 522 individuals without neurodegenerative disorders were enrolled in this study to explore the GLE1 gene contribution to ALS in the Chinese population. All 16 exons and the flanking intron of GLE1 were screened by Sanger sequencing. In total, we identified seven rare GLE1 coding variants, including one novel nonsense mutation and six rare missense mutations in 628 ALS patients. The frequency of GLE1 LOF mutations was 0.16% (1/628) among Chinese sALS patients, implying that it is an uncommon genetic determinant of ALS in Chinese patients. Additionally, the rare missense variants in the hCG1-binding domain of GLE1 impairing the distribution of the hGle1B isoform at the nuclear pore complex (NPC) region may be involved in the pathogenesis of ALS.https://www.frontiersin.org/articles/10.3389/fnins.2021.595775/fullamyotrophic lateral sclerosisGLE1loss-of-function mutationOPTNoligogenic inheritance of ALS
collection DOAJ
language English
format Article
sources DOAJ
author Yanran Li
Bo Sun
Zhanjun Wang
Zhengqing He
Fei Yang
Hongfen Wang
Fang Cui
Zhaohui Chen
Li Ling
Chaodong Wang
Xusheng Huang
spellingShingle Yanran Li
Bo Sun
Zhanjun Wang
Zhengqing He
Fei Yang
Hongfen Wang
Fang Cui
Zhaohui Chen
Li Ling
Chaodong Wang
Xusheng Huang
Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients
Frontiers in Neuroscience
amyotrophic lateral sclerosis
GLE1
loss-of-function mutation
OPTN
oligogenic inheritance of ALS
author_facet Yanran Li
Bo Sun
Zhanjun Wang
Zhengqing He
Fei Yang
Hongfen Wang
Fang Cui
Zhaohui Chen
Li Ling
Chaodong Wang
Xusheng Huang
author_sort Yanran Li
title Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients
title_short Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients
title_full Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients
title_fullStr Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients
title_full_unstemmed Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients
title_sort mutation screening of the gle1 gene in a large chinese cohort of amyotrophic lateral sclerosis patients
publisher Frontiers Media S.A.
series Frontiers in Neuroscience
issn 1662-453X
publishDate 2021-05-01
description Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease involving the upper and lower motor neurons of the spinal cord, brainstem, and cerebral cortex. At least 30 genes have been implicated in familial ALS (fALS) and sporadic ALS (sALS). Kaneb et al. (2015) first carried out a large-scale sequencing study in ALS patients and identified two loss-of-function (LOF) variants in the GLE1 gene. The LOF mutation-induced disruption of RNA metabolism through the haploinsufficiency mechanism is implicated in ALS pathogenesis. A total of 628 ALS patients and 522 individuals without neurodegenerative disorders were enrolled in this study to explore the GLE1 gene contribution to ALS in the Chinese population. All 16 exons and the flanking intron of GLE1 were screened by Sanger sequencing. In total, we identified seven rare GLE1 coding variants, including one novel nonsense mutation and six rare missense mutations in 628 ALS patients. The frequency of GLE1 LOF mutations was 0.16% (1/628) among Chinese sALS patients, implying that it is an uncommon genetic determinant of ALS in Chinese patients. Additionally, the rare missense variants in the hCG1-binding domain of GLE1 impairing the distribution of the hGle1B isoform at the nuclear pore complex (NPC) region may be involved in the pathogenesis of ALS.
topic amyotrophic lateral sclerosis
GLE1
loss-of-function mutation
OPTN
oligogenic inheritance of ALS
url https://www.frontiersin.org/articles/10.3389/fnins.2021.595775/full
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