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Translational Neurodegeneration
Published in: Translational Neurodegeneration 1/2019

Open Access 01-12-2019 | Spastic Paraplegia | Research

Clinical features and genetic spectrum in Chinese patients with recessive hereditary spastic paraplegia

Authors: Qiao Wei, Hai-Lin Dong, Li-Ying Pan, Cong-Xin Chen, Yang-Tian Yan, Rou-Min Wang, Hong-Fu Li, Zhi-Jun Liu, Qing-Qing Tao, Zhi-Ying Wu

Published in: Translational Neurodegeneration | Issue 1/2019

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Abstract

Background

Although many causative genes of hereditary spastic paraplegia (HSP) have been uncovered in recent years, there are still approximately 50% of HSP patients without genetically diagnosis, especially in autosomal recessive (AR) HSP patients. Rare studies have been performed to determine the genetic spectrum and clinical profiles of recessive HSP patients in the Chinese population.

Methods

In this study, we investigated 24 Chinese index AR/sporadic patients by targeted next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Further functional studies were performed to identify pathogenicity of those uncertain significance variants.

Results

We identified 11 mutations in HSP related genes including 7 novel mutations, including two (p.V1979_L1980delinsX, p.F2343 fs) in SPG11, two (p.T55 M, p.S308 T) in AP5Z1, one (p.S242 N) in ALDH18A1, one (p.D597fs) in GBA2, and one (p.Q486X) in ATP13A2 in 8 index patients and their family members. Mutations in ALDH18A1, AP5Z1, CAPN1 and ATP13A2 genes were firstly reported in the Chinese population. Furthermore, the clinical phenotypes of the patients carrying mutations were described in detail. The mutation (p.S242 N) in ALDH18A1 decreased enzyme activity of P5CS and mutations (p.T55 M, p.S308 T) in AP5Z1 induced lysosomal dysfunction.

Conclusion

Our results expanded the genetic spectrum and clinical profiles of AR-HSP patients and further demonstrated the efficiency and reliability of targeted NGS diagnosing suspected HSP patients.
Appendix
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Metadata
Title
Clinical features and genetic spectrum in Chinese patients with recessive hereditary spastic paraplegia
Authors
Qiao Wei
Hai-Lin Dong
Li-Ying Pan
Cong-Xin Chen
Yang-Tian Yan
Rou-Min Wang
Hong-Fu Li
Zhi-Jun Liu
Qing-Qing Tao
Zhi-Ying Wu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Translational Neurodegeneration / Issue 1/2019
Electronic ISSN: 2047-9158
DOI
https://doi.org/10.1186/s40035-019-0157-9

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