Wang J, Bu WT, Zhu MJ, Tang JY, Liu XM. Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia: A case report. World J Clin Cases 2023; 11(14): 3288-3294 [PMID: 37274038 DOI: 10.12998/wjcc.v11.i14.3288]
Corresponding Author of This Article
Xiao-Min Liu, PhD, Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan 250014, Shandong Province, China. lxmywc@163.com
Research Domain of This Article
Genetics & Heredity
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Cases. May 16, 2023; 11(14): 3288-3294 Published online May 16, 2023. doi: 10.12998/wjcc.v11.i14.3288
Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia: A case report
Jie Wang, Wei-Ting Bu, Mei-Jia Zhu, Ji-You Tang, Xiao-Min Liu
Jie Wang, Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
Wei-Ting Bu, Department of Neurology, Shandong Provincial Qianfoshan Hospital, Weifang Medical University, Jinan 250014, Shandong Province, China
Mei-Jia Zhu, Ji-You Tang, Xiao-Min Liu, Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, Shandong Province, China
Author contributions: Wang J wrote the manuscript; Liu XM and Zhu MJ performed the neurological examinations; Wang J and Liu XM assessed the mutation and analyzed neuroimages; Liu XM and Tang JY designed the report; Wang J and Bu WT drafted the manuscript; and all authors read and approved the final version of the manuscript.
Informed consent statement: This study was approved by the Ethics Committee of Shandong First Medical University. Informed consent was obtained for the publication of relevant clinical information and photographs.
Conflict-of-interest statement: All authors report having no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Min Liu, PhD, Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan 250014, Shandong Province, China. lxmywc@163.com
Received: January 6, 2023 Peer-review started: January 6, 2023 First decision: February 8, 2023 Revised: March 15, 2023 Accepted: April 12, 2023 Article in press: April 12, 2023 Published online: May 16, 2023
Abstract
BACKGROUND
Hereditary spastic paraplegia (HSP) is a group of neurogenetic diseases of the corticospinal tract, accompanied by distinct spasticity and weakness of the lower extremities. Mutations in the spastic paraplegia type 4 (SPG4) gene, encoding the spastin protein, are the major cause of the disease. This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene.
CASE SUMMARY
A 44-year-old male was admitted to our hospital for long-term right lower limb weakness, leg stiffness, and unstable walking. His symptoms gradually worsened, while no obvious muscle atrophy in the lower limbs was found. Neurological examinations revealed that the muscle strength of the lower limbs was normal, and knee reflex hyperreflexia and bilateral positive Babinski signs were detected. Members of his family also had the same symptoms. Using mutation analysis, a novel heterozygous duplication mutation, c.1053dupA, p. (Gln352Thrfs*15), was identified in the SPG4 gene in this family.
CONCLUSION
A Chinese family with HSP had a novel mutation of the SPG4 gene, which is autosomal dominant and inherited as pure HSP. The age of onset, sex distribution, and clinical manifestations of all existing living patients in this family were analyzed. The findings may extend the current knowledge on the existing mutations in the SPG4 gene.
Core Tip: It is difficult to distinguish hereditary spastic paraplegia (HSP) from other spasticity-related genetic diseases because the different affected genes lead to large differences in the pathogenic mechanisms, clinical features, and imaging abnormalities of HSP. Therefore, genetic testing is important for the diagnosis and typing of HSP. A Chinese HSP male patient was identified, and pedigree surveys of his relatives were performed. Furthermore, genomic DNA was extracted for whole-exome sequencing, and pathogenic variants were screened by bioinformatics methods and verified using Sanger sequencing. A novel heterozygous duplication mutation, c.1053dupA, p. (Gln352Thrfs*15), was identified in the SPG4 gene in this family.
