遗传性痉挛性截瘫病患家系基因诊断1例并文献研究

朱芯潼; 郭洪

doi:10.16016/j.2097-0927.202210186

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遗传性痉挛性截瘫病患家系基因诊断1例并文献研究

临床医学 | 更新时间：2026-01-09

- 遗传性痉挛性截瘫病患家系基因诊断1例并文献研究
- Genetic diagnosis of hereditary spastic paraplegia in a family: one case report and literature review
- 陆军军医大学学报 2023年45卷第8期页码：847-853
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)基础医学院遗传学教研室
  2.400037 重庆，陆军军医大学(第三军医大学)第二附属医院妇产科
- 作者简介：
  
  [郭洪，E-mail: guohong02@gmail.comGUO Hong, E-mail: guohong02@gmail.com
- 基金信息：
  
  国家自然科学基金面上项目(82171840);重庆市自然科学基金(cstc2021jcyj-msxmX0281)
- DOI：10.16016/j.2097-0927.202210186
  中图分类号： R394.1;R596.1;R681.1
- 收稿：2022-10-21，
  
  修回：2022-11-08，
  
  纸质出版：2023-04-30
- 稿件说明：
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朱芯潼, 郭洪. 遗传性痉挛性截瘫病患家系基因诊断1例并文献研究[J]. 陆军军医大学学报, 2023,45(8):847-853.

Xintong ZHU, Hong GUO. Genetic diagnosis of hereditary spastic paraplegia in a family: one case report and literature review[J]. Journal of Army Medical University, 2023, 45(8): 847-853.
朱芯潼, 郭洪. 遗传性痉挛性截瘫病患家系基因诊断1例并文献研究[J]. 陆军军医大学学报, 2023,45(8):847-853. DOI： 10.16016/j.2097-0927.202210186.

Xintong ZHU, Hong GUO. Genetic diagnosis of hereditary spastic paraplegia in a family: one case report and literature review[J]. Journal of Army Medical University, 2023, 45(8): 847-853. DOI： 10.16016/j.2097-0927.202210186.

摘要

目的

对1例遗传性痉挛性截瘫病患进行家系遗传学分析，为研究遗传性痉挛性截瘫的发病机制和治疗方法提供理论依据。

方法

2021年4月30日于陆军军医大学第二附属医院遗传咨询门诊收集患者信息，经知情同意后对患者进行家系成员临床资料调查及系谱分析，提取其外周血基因组DNA进行遗传学检测及分析。

结果

患者以进行性下肢痉挛与无力为主要表现，影像学检查提示薄胼胝体，通过全外显子组测序及Sanger测序确诊患者

SPG 11

基因存在双等位缺失c.733_734del(p.M245Vfs

2)，该变异根据ACMG指南，判定为致病性变异，诊断为遗传性痉挛性截瘫11型，患者家系中有7名成员携带此突变。

结论

该家系是由

SPG 11

基因致病性纯合缺失突变c.733_734del(p.M245Vfs

2)而引起的遗传性痉挛性截瘫11型，患者具有遗传性痉挛性截瘫典型的临床表现特征，分子遗传学技术可对家系成员进行基因确诊和症状前诊断。

Abstract

Objective

To genetically analyze a family with hereditary spastic paraplegia in order to provide theoretical basis for the pathogenesis and treatment of the disease.

Methods

Clinical data of a male patient suffering from the hereditary disease admitted to the Genetic Counseling Clinic of the Second Affiliated Hospital on April 30

2021 were collected. After the patient and his family members signed our informed consent

a family survey and genealogical analysis was conducted

and their peripheral blood genomic DNA was extracted for genetic testing and analysis.

Results

The patient manifested with progressive lower limb spasticity and weakness

and imaging suggested thin corpus callosum. Whole exome sequencing and Sanger sequencing indicated that the patient was identified with a double allelic deletion c.733_734del (p.M245Vfs

2) in the

SPG 11

gene

and this mutation was determined to be pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines. The patient was diagnosed with hereditary spastic paraplegia type 11

and his 7 family members carred this mutation.

Conclusion

This family is a hereditary spastic paraplegia type 11 caused by the pathogenic pure de

letion mutation c.733_734del(p.M245Vfs

2) in the

SPG 11

gene. The patient has typical clinical manifestations of the disease. It is very important to use molecular genetic techniques for genetic confirmation and pre-symptomatic diagnosis of family members.

关键词

Keywords

references

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STEVANIN G, SANTORELLI F M, AZZEDINE H, et al . Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum[J ] . Nat Genet, 2007, 39(3): 366-372. DOI: 10.1038/ng1980.

POZNER T, REGENSBURGER M, ENGELHORN T, et al . Janus -faced spatacsin (SPG11): involvement in neuro-development and multisystem neurodegeneration[J ] . Brain, 2020, 143(8): 2369-2379. DOI: 10.1093/brain/awaa099..

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HIRST J, HESKETH G G, GINGRAS A C, et al . Rag GTPases and phosphatidylinositol 3-phosphate mediate recruitment of the AP-5/SPG11/SPG15 complex[J ] . J Cell Biol, 2021, 220(2): e202002075. DOI: 10.1083/jcb.202002075.

HIRST J, ITZHAK D N, ANTROBUS R, et al . Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval[J ] . PLoS Biol, 2018, 16(1): e2004411. DOI: 10.1371/journal.pbio.2004411.

DENEUBOURG C, RAMM M, SMITH L J, et al . The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy[J ] . Autophagy, 2022, 18(3): 496-517. DOI: 10.1080/15548627.2021.1943177.

SHRIBMAN S, REID E, CROSBY A H, et al . Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches[J ] . Lancet Neurology, 2019, 18(12): 1136-1146. DOI: 10.1016/S1474-4422(19)30235-2.

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