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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.776831/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T04:08:48Z |
| format | Article |
| id | doaj.art-05e392a11dd147c9a190895c52b89503 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-20T04:08:48Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-05e392a11dd147c9a190895c52b895032022-12-21T19:53:58ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-11-011210.3389/fgene.2021.776831776831Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA PhenotypeXinmei Wen0Wenjia Zhu1Nan L. Xia2Qianwen Li3Qianwen Li4Li Di5Shu Zhang6Hai Chen7Yan Lu8Min Wang9Min Xu10Suobin Wang11Xin-Ming Shen12Jie Lu13Jie Lu14Yuwei Da15Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaDepartment of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN, United StatesDepartment of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaAmyotrophic 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.https://www.frontiersin.org/articles/10.3389/fgene.2021.776831/fullamyotrophic lateral sclerosisSOD1lower motor neuronprogressive muscular atrophyrapid progression |
| spellingShingle | 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 Frontiers in Genetics amyotrophic lateral sclerosis SOD1 lower motor neuron progressive muscular atrophy rapid progression |
| title | 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_short | 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 |
| topic | amyotrophic lateral sclerosis SOD1 lower motor neuron progressive muscular atrophy rapid progression |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.776831/full |
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