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Genetic analysis in Chinese patients with familial or young-onset amyotrophic lateral sclerosis

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A Correction to this article was published on 22 January 2022

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Abstract

Objective

The aim of our study was to investigate the genetic characteristics in patients with familial or young-onset amyotrophic lateral sclerosis (ALS) in a Chinese center.

Methods

Patients with familial or young-onset (age of onset < 45 years old) ALS were reviewed. The clinical data was collected. Whole-exome sequencing was performed to identify the disease-associated variants. Single-nucleotide variants and small insertions/deletions were further predicted with silico tools and compared to the Single Nucleotide Polymorphism Database, Exome Aggregation Consortium, and the 1000 Genomes Project. The evolutionary conservations were estimated, and the structures of proteins were constructed by Swiss-Model server. Immunohistochemistry was used to confirm the misfolded SOD1 protein.

Results

Three familial ALS and 5 young-onset ALS were enrolled. Genetic analysis identified related variants of SOD1 (4/6, 66.7%), FUS (1/6, 16.7%), and NEK1 (1/6, 16.7%) in 6 patients. Three of them were familial probands (3/3, 100%), and the others were sporadic young-onset patients (3/5, 60%). NEK1 c.290G > A mutation (NM_012224.2 exon4) in a patient with familial ALS and SOD1 c.362A > G mutation (NM_000454 exon5) in a young-onset ALS patient were novel. The novel mutations were predicted to be deleterious, affected evolutionarily highly conserved amino acid residue and the formation of hydrogen bonds between the mutated site and its surrounding amino acid residues. Misfolded SOD1 protein was identified in patient with SOD1 c.362A > G mutation.

Conclusions

Two novel mutations were detected in our patients. Patients with familial or young-onset ALS often carried related gene mutations, and genetic sequencing should be thus routinely performed.

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Acknowledgements

We thank the subjects for their participation in this study.

Funding

This work was supported by the Shanxi Science and Technology Department under grant no. 201704D13111584.

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Authors and Affiliations

  1. Department of Neurology, First Hospital, Shanxi Medical University, No.85, Jiefang South Street, Taiyuan, 030000, People’s Republic of China

    Jing Ma, Xiaomin Pang, Shan Huang, Jing Zhang, Juan Wang, Rongjuan Zhao, Xueli Chang, Junhong Guo & Wei Zhang

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  1. Jing Ma
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  2. Xiaomin Pang
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  3. Shan Huang
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  4. Jing Zhang
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  5. Juan Wang
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  8. Junhong Guo
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  9. Wei Zhang
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Contributions

MJ, ZW, and GJ designed the study; ZJ, PXM, and WJ performed EMG; CXL and HS helped to collect the data; MJ and ZW analyzed the data; MJ wrote the manuscript.

Corresponding author

Correspondence to Wei Zhang.

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Ethical approval

Our ethics committee approved the study. Informed consent for participation, sample collection, and medical records review was obtained from the participants.

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The authors declare no competing interests.

Informed consent

Informed consent for participation, sample collection, and medical records review was obtained from the participants.

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Ma, J., Pang, X., Huang, S. et al. Genetic analysis in Chinese patients with familial or young-onset amyotrophic lateral sclerosis. Neurol Sci 43, 2579–2587 (2022). https://doi.org/10.1007/s10072-021-05634-z

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  • DOI: https://doi.org/10.1007/s10072-021-05634-z

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