Hand‐onset weakness is a common feature of ALS patients with a NEK1 loss‐of‐function variant
Abstract Objective The NEK1 gene has been recently implicated in amyotrophic lateral sclerosis (ALS). This study aims to assess the influence of NEK1 variants on the occurrence of ALS and investigate the spectrum and clinical features of NEK1 loss‐of‐function (LOF) variants in a Taiwanese ALS cohort...
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Online Access: | https://doi.org/10.1002/acn3.51064 |
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doaj-c5820645fa7543aa945af2d359a936552021-05-03T00:31:07ZengWileyAnnals of Clinical and Translational Neurology2328-95032020-06-017696597110.1002/acn3.51064Hand‐onset weakness is a common feature of ALS patients with a NEK1 loss‐of‐function variantYu‐Shuen Tsai0Kon‐Ping Lin1Kang‐Yang Jih2Pei‐Chien Tsai3Yi‐Chu Liao4Yi‐Chung Lee5Center for Systems and Synthetic Biology National Yang‐Ming University Taipei TaiwanDepartment of Neurology Neurological InstituteTaipei Veterans General Hospital Taipei TaiwanDepartment of Neurology Neurological InstituteTaipei Veterans General Hospital Taipei TaiwanDepartment of Life Sciences National Chung Hsing University Taichung TaiwanDepartment of Neurology Neurological InstituteTaipei Veterans General Hospital Taipei TaiwanDepartment of Neurology Neurological InstituteTaipei Veterans General Hospital Taipei TaiwanAbstract Objective The NEK1 gene has been recently implicated in amyotrophic lateral sclerosis (ALS). This study aims to assess the influence of NEK1 variants on the occurrence of ALS and investigate the spectrum and clinical features of NEK1 loss‐of‐function (LOF) variants in a Taiwanese ALS cohort. Methods We screened 325 unrelated ALS patients for coding variants in NEK1 by targeted resequencing and queried the Taiwan Biobank database for NEK1 coding variants in 1000 Taiwanese healthy individuals. The clinical features of the patients with a NEK1 LOF variant were analyzed. Results Six patients and two healthy individuals carried NEK1 LOF variants. The rare missense variants with minor allele frequencies <0.1% in Taiwanese population were present in 2.8% of the ALS patients and 1.6% of the healthy subjects. NEK1 LOF variants, but not rare missense variants, are significantly enriched in the ALS patients (P = 0.0037 and 0.24, Fisher’s exact test). The odds ratio of an individual carrying a NEK1 LOF variant to develop ALS is 9.39 (95% confidence interval: 1.88–46.7). All the six patients carrying a NEK1 LOF variant had a hand‐onset ALS with an onset age from 52 to 64 years. Comparing with ALS patients without a NEK1 LOF variant, patients with a NEK1 LOF variant tend to have a hand‐onset disease (P = 0.0008, Fisher’s exact test). Interpretation Our study supports the pathogenic role of NEK1 LOF variants and demonstrates their spectrum and clinical features in a Taiwanese cohort with ALS.https://doi.org/10.1002/acn3.51064 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu‐Shuen Tsai Kon‐Ping Lin Kang‐Yang Jih Pei‐Chien Tsai Yi‐Chu Liao Yi‐Chung Lee |
spellingShingle |
Yu‐Shuen Tsai Kon‐Ping Lin Kang‐Yang Jih Pei‐Chien Tsai Yi‐Chu Liao Yi‐Chung Lee Hand‐onset weakness is a common feature of ALS patients with a NEK1 loss‐of‐function variant Annals of Clinical and Translational Neurology |
author_facet |
Yu‐Shuen Tsai Kon‐Ping Lin Kang‐Yang Jih Pei‐Chien Tsai Yi‐Chu Liao Yi‐Chung Lee |
author_sort |
Yu‐Shuen Tsai |
title |
Hand‐onset weakness is a common feature of ALS patients with a NEK1 loss‐of‐function variant |
title_short |
Hand‐onset weakness is a common feature of ALS patients with a NEK1 loss‐of‐function variant |
title_full |
Hand‐onset weakness is a common feature of ALS patients with a NEK1 loss‐of‐function variant |
title_fullStr |
Hand‐onset weakness is a common feature of ALS patients with a NEK1 loss‐of‐function variant |
title_full_unstemmed |
Hand‐onset weakness is a common feature of ALS patients with a NEK1 loss‐of‐function variant |
title_sort |
hand‐onset weakness is a common feature of als patients with a nek1 loss‐of‐function variant |
publisher |
Wiley |
series |
Annals of Clinical and Translational Neurology |
issn |
2328-9503 |
publishDate |
2020-06-01 |
description |
Abstract Objective The NEK1 gene has been recently implicated in amyotrophic lateral sclerosis (ALS). This study aims to assess the influence of NEK1 variants on the occurrence of ALS and investigate the spectrum and clinical features of NEK1 loss‐of‐function (LOF) variants in a Taiwanese ALS cohort. Methods We screened 325 unrelated ALS patients for coding variants in NEK1 by targeted resequencing and queried the Taiwan Biobank database for NEK1 coding variants in 1000 Taiwanese healthy individuals. The clinical features of the patients with a NEK1 LOF variant were analyzed. Results Six patients and two healthy individuals carried NEK1 LOF variants. The rare missense variants with minor allele frequencies <0.1% in Taiwanese population were present in 2.8% of the ALS patients and 1.6% of the healthy subjects. NEK1 LOF variants, but not rare missense variants, are significantly enriched in the ALS patients (P = 0.0037 and 0.24, Fisher’s exact test). The odds ratio of an individual carrying a NEK1 LOF variant to develop ALS is 9.39 (95% confidence interval: 1.88–46.7). All the six patients carrying a NEK1 LOF variant had a hand‐onset ALS with an onset age from 52 to 64 years. Comparing with ALS patients without a NEK1 LOF variant, patients with a NEK1 LOF variant tend to have a hand‐onset disease (P = 0.0008, Fisher’s exact test). Interpretation Our study supports the pathogenic role of NEK1 LOF variants and demonstrates their spectrum and clinical features in a Taiwanese cohort with ALS. |
url |
https://doi.org/10.1002/acn3.51064 |
work_keys_str_mv |
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