Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype

Wen, Xinmei and Zhu, Wenjia and Xia, Nan L. and Li, Qianwen and Di, Li and Zhang, Shu and Chen, Hai and Lu, Yan and Wang, Min and Xu, Min and Wang, Suobin and Shen, Xin-Ming and Lu, Jie and Da, Yuwei (2021) Missense Mutations of Codon 116 in the SOD1 Gene Cause Rapid Progressive Familial ALS and Predict Short Viability With PMA Phenotype. Frontiers in Genetics, 12. ISSN 1664-8021

[thumbnail of pubmed-zip/versions/3/package-entries/fgene-12-776831-r2/fgene-12-776831.pdf] Text
pubmed-zip/versions/3/package-entries/fgene-12-776831-r2/fgene-12-776831.pdf - Published Version

Download (1MB)

Abstract

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.

Item Type: Article
Subjects: Research Asian Plos > Medical Science
Depositing User: Unnamed user with email support@research.asianplos.com
Date Deposited: 27 Jan 2023 08:58
Last Modified: 17 Oct 2024 05:02
URI: http://abstract.stmdigitallibrary.com/id/eprint/27

Actions (login required)

View Item
View Item