Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, characterized by a great variety of both clinical presentations and genetic causes. Previous studies had identified two different missense mutations in SOD1 (p.R116C and p.R116G) causing familial ALS. In this study,...
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2021
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oai:doaj.org-article:05e392a11dd147c9a190895c52b895032021-11-17T10:39:49ZMissense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype1664-802110.3389/fgene.2021.776831https://doaj.org/article/05e392a11dd147c9a190895c52b895032021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.776831/fullhttps://doaj.org/toc/1664-8021Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, characterized by a great variety of both clinical presentations and genetic causes. Previous studies had identified two different missense mutations in SOD1 (p.R116C and p.R116G) causing familial ALS. In this study, we report a novel heterozygous missense mutation in the SOD1 gene (p.R116S) in a family with inherited ALS manifested as fast-deteriorating pure lower motor neuron symptoms. The patient displayed similar clinical picture and prognostic value to previous reported cases with different R116 substitution mutations. Modeling of all R116 substitutions in the resolved SOD1 protein structure revealed a shared mechanism with destroyed hydrogen bonds between R116 and other two residues, which might lead to protein unfolding and oligomer formation, ultimately conferring neurotoxicity.Xinmei WenWenjia ZhuNan L. XiaQianwen LiQianwen LiLi DiShu ZhangHai ChenYan LuMin WangMin XuSuobin WangXin-Ming ShenJie LuJie LuYuwei DaFrontiers Media S.A.articleamyotrophic lateral sclerosisSOD1lower motor neuronprogressive muscular atrophyrapid progressionGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021) |
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| topic |
amyotrophic lateral sclerosis SOD1 lower motor neuron progressive muscular atrophy rapid progression Genetics QH426-470 |
| spellingShingle |
amyotrophic lateral sclerosis SOD1 lower motor neuron progressive muscular atrophy rapid progression Genetics QH426-470 Xinmei Wen Wenjia Zhu Nan L. Xia Qianwen Li Qianwen Li Li Di Shu Zhang Hai Chen Yan Lu Min Wang Min Xu Suobin Wang Xin-Ming Shen Jie Lu Jie Lu Yuwei Da Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype |
| description |
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, characterized by a great variety of both clinical presentations and genetic causes. Previous studies had identified two different missense mutations in SOD1 (p.R116C and p.R116G) causing familial ALS. In this study, we report a novel heterozygous missense mutation in the SOD1 gene (p.R116S) in a family with inherited ALS manifested as fast-deteriorating pure lower motor neuron symptoms. The patient displayed similar clinical picture and prognostic value to previous reported cases with different R116 substitution mutations. Modeling of all R116 substitutions in the resolved SOD1 protein structure revealed a shared mechanism with destroyed hydrogen bonds between R116 and other two residues, which might lead to protein unfolding and oligomer formation, ultimately conferring neurotoxicity. |
| format |
article |
| author |
Xinmei Wen Wenjia Zhu Nan L. Xia Qianwen Li Qianwen Li Li Di Shu Zhang Hai Chen Yan Lu Min Wang Min Xu Suobin Wang Xin-Ming Shen Jie Lu Jie Lu Yuwei Da |
| author_facet |
Xinmei Wen Wenjia Zhu Nan L. Xia Qianwen Li Qianwen Li Li Di Shu Zhang Hai Chen Yan Lu Min Wang Min Xu Suobin Wang Xin-Ming Shen Jie Lu Jie Lu Yuwei Da |
| author_sort |
Xinmei Wen |
| title |
Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype |
| title_short |
Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype |
| title_full |
Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype |
| title_fullStr |
Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype |
| title_full_unstemmed |
Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype |
| title_sort |
missense mutations of codon 116 in the sod1 gene cause rapid progressive familial als and predict short viability with pma phenotype |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/05e392a11dd147c9a190895c52b89503 |
| work_keys_str_mv |
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