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Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report
BACKGROUND: Autosomal recessive hereditary spastic paraplegias (ARHSPs) are a group of clinically and genetically heterogeneous neurodegenerative diseases with progressive spasticity and weakness in the lower limbs. Mutations in the Spastic Paraplegia gene 7 (SPG7) account for about 5–21% of ARHSP c...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263041/ https://www.ncbi.nlm.nih.gov/pubmed/30497413 http://dx.doi.org/10.1186/s12883-018-1199-9 |
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author | Zhang, Xiaoqian Zhang, Lei Wu, Yanqing Li, Gang Chen, Shengcai Xia, Yuanpeng Li, Hongge |
author_facet | Zhang, Xiaoqian Zhang, Lei Wu, Yanqing Li, Gang Chen, Shengcai Xia, Yuanpeng Li, Hongge |
author_sort | Zhang, Xiaoqian |
collection | PubMed |
description | BACKGROUND: Autosomal recessive hereditary spastic paraplegias (ARHSPs) are a group of clinically and genetically heterogeneous neurodegenerative diseases with progressive spasticity and weakness in the lower limbs. Mutations in the Spastic Paraplegia gene 7 (SPG7) account for about 5–21% of ARHSP cases. However, in Asians, few reports about the mutations exist. In this study, we firstly report a novel finding from a Chinese family with compound heterozygous SPG7 mutations, in which three siblings were affected with a complicated form of ARHSP. CASE PRESENTATION: A 56-year-old man presented with progressive stiffness, weakness and ataxia in the lower limbs. Two sisters of him had similar symptoms and dysarthria. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy in each of the patients. Genetic analysis, which exerted a targeted next generation sequencing (NGS) panel covering 917 comprehensive ataxia genes to the proband, followed by Sanger sequencing of candidate genes in other eight family members, was used to find the etiology of the disease. Ultimately, we identified compound heterozygous SPG7 mutations with two mutations: (c.1150_1150-1insCTAC and c.2062C > T, p.Arg688Trp) and one single nucleotide polymorphism (c.2063G > A, p.Arg688Gln). CONCLUSIONS: The four bases insertion mutation (4bIM) was predicted to cause frameshift mutation or affect the splicing, and the last two variants were led to a stop codon mutation (p.Arg688Ter). As located in highly conserved positions and encoded paraplegin, the mutations were speculated to result in a truncated or defective protein and would be pathogenic factors of the disease. This paper proves to be the first case report of SPG7 mutation in ARHSP reported in Chinese population. Our findings widen the spectrum of SPG7 mutations of ARHSP and indicate that the SPG7 mutation is an important cause of adult-onset undiagnosed ataxia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12883-018-1199-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6263041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-62630412018-12-05 Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report Zhang, Xiaoqian Zhang, Lei Wu, Yanqing Li, Gang Chen, Shengcai Xia, Yuanpeng Li, Hongge BMC Neurol Case Report BACKGROUND: Autosomal recessive hereditary spastic paraplegias (ARHSPs) are a group of clinically and genetically heterogeneous neurodegenerative diseases with progressive spasticity and weakness in the lower limbs. Mutations in the Spastic Paraplegia gene 7 (SPG7) account for about 5–21% of ARHSP cases. However, in Asians, few reports about the mutations exist. In this study, we firstly report a novel finding from a Chinese family with compound heterozygous SPG7 mutations, in which three siblings were affected with a complicated form of ARHSP. CASE PRESENTATION: A 56-year-old man presented with progressive stiffness, weakness and ataxia in the lower limbs. Two sisters of him had similar symptoms and dysarthria. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy in each of the patients. Genetic analysis, which exerted a targeted next generation sequencing (NGS) panel covering 917 comprehensive ataxia genes to the proband, followed by Sanger sequencing of candidate genes in other eight family members, was used to find the etiology of the disease. Ultimately, we identified compound heterozygous SPG7 mutations with two mutations: (c.1150_1150-1insCTAC and c.2062C > T, p.Arg688Trp) and one single nucleotide polymorphism (c.2063G > A, p.Arg688Gln). CONCLUSIONS: The four bases insertion mutation (4bIM) was predicted to cause frameshift mutation or affect the splicing, and the last two variants were led to a stop codon mutation (p.Arg688Ter). As located in highly conserved positions and encoded paraplegin, the mutations were speculated to result in a truncated or defective protein and would be pathogenic factors of the disease. This paper proves to be the first case report of SPG7 mutation in ARHSP reported in Chinese population. Our findings widen the spectrum of SPG7 mutations of ARHSP and indicate that the SPG7 mutation is an important cause of adult-onset undiagnosed ataxia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12883-018-1199-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-29 /pmc/articles/PMC6263041/ /pubmed/30497413 http://dx.doi.org/10.1186/s12883-018-1199-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Case Report Zhang, Xiaoqian Zhang, Lei Wu, Yanqing Li, Gang Chen, Shengcai Xia, Yuanpeng Li, Hongge Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report |
title | Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report |
title_full | Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report |
title_fullStr | Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report |
title_full_unstemmed | Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report |
title_short | Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report |
title_sort | identification of novel compound heterozygous spg7 mutations-related hereditary spastic paraplegia in a chinese family: a case report |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263041/ https://www.ncbi.nlm.nih.gov/pubmed/30497413 http://dx.doi.org/10.1186/s12883-018-1199-9 |
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