The investigation of genetic and clinical features in patients with hereditary spastic paraplegia in central‐Southern China

Wang, Chen; Zhang, Yunjian; Xu, Cihao; Li, De; Liu, Zhijun; Wu, Yan

doi:10.1002/mgg3.1627

Cited by 7 publications

(9 citation statements)

References 28 publications

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“…SPG26/B4GALNT1 [81] and mitochondrial DNA for oxidative phosphorylation mitoribosomes (SPG55/C12ORF65) [82] are found at 12q13.3 and q24.31. Mutations in these genes are linked with peripheral neuropathies, optic zone atrophy, cognitive disabilities, and pyramidal characteristics.…”

Section: Chromosome 12mentioning

confidence: 99%

Hereditary Spastic Paraplegia: An Update

Meyyazhagan

Orlacchio

2022

IJMS

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Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. HSP is categorised based on inheritance, the phenotypic characters, and the mode of molecular pathophysiology, with frequent degeneration in the axon of cervical and thoracic spinal cord’s lateral region, comprising the corticospinal routes. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. Though modern medical interventions help recognize and manage the disorder, the symptomatic measures remain below satisfaction. The present review assimilates the available data on HSP and lists down the chromosomes involved in its pathophysiology and the mutations observed in the respective genes on the chromosomes. It also sheds light on the treatment available along with the oral/intrathecal medications, physical therapies, and surgical interventions. Finally, we have discussed the related diagnostic techniques as well as the linked pharmacogenomics studies under future perspectives.

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Section: Chromosome 12mentioning

confidence: 99%

Hereditary Spastic Paraplegia: An Update

Meyyazhagan

Orlacchio

2022

IJMS

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“…The missense variant had a low sequency in the database, and prediction software suggests that this mutation can cause destructive effects on protein function. SPG26 is one of the causes of AR-HSP, and few cases have been reported worldwide (Wang et al, 2021). The AAO of our case was 42 years.…”

Section: Genetic Analysis and Genotype Distributionmentioning

confidence: 52%

Clinical features and genetic spectrum of Chinese patients with hereditary spastic paraplegia: A 14-year study

He²,

Liu³

et al. 2023

Front. Genet.

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Background: Hereditary spastic paraplegia (HSP) constitutes a group of clinically and genetically rare neurodegenerative diseases characterized by progressive corticospinal tract degeneration. The phenotypes and genotypes of HSP are still expanding. In this study, we aimed to analyse the differential diagnosis, clinical features, and genetic distributions of a Chinese HSP patients in a 14-year cohort and to improve our understanding of the disease.Methods: The clinical data of patients with a primary diagnosis of HSP at the initial visit to the Department of the Neurology, Peking University Third Hospital, from 2008 to 2022 were retrospectively collected. Next-generation sequencing gene panels (NGS) combined with a multiplex ligation-amplification assay (MLPA) were conducted. Epidemiological and clinical features and candidate variants in HSP-related genes were analyzed and summarized.Results: 54 cases (probands from 25 different pedigrees and 29 sporadic cases) from 95 patients with a primary diagnosis of HSP were finally confirmed to have a clinical diagnosis of HSP based on clinical criteria, including their clinical findings, family history and long-term follow-up. Earlier disease onset was associated with longer diagnostic delay and longer disease duration and was associated with a lower risk of loss of ability to walk independently. In addition, 20 candidate variants in reported HSP-related genes were identified in these clinically diagnosed HSP patients, including variants in SPAST, ALT1, WASHC5, SPG11, B4GALNT1, and REEP1. The genetic diagnostic rate in these 54 patients was 35.18%.Conclusion: Hereditary spastic paraplegia has high clinical and genetic heterogeneity and is prone to misdiagnosis. Long-term follow-up and genetic testing can partially assist in diagnosing HSP. Our study summarized the clinical features of Chinese HSP patients in a 14-year cohort, expanded the genotype spectrum, and improved our understanding of the disease.

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“…It is possible that neurosteroid progesterone and oestrogens could protect females. Protective factors could delay onset of the disorder, but once started, its evolution is more rapid and severe than in males [14][15][16][17] .…”

Section: Discussionmentioning

confidence: 99%

A SPAST gene-related hereditary spastic paraplegia type 4 family: Identification by a novel mutation

Zhang

wang

2022

Preprint

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Objective: The aim of this study was to confirm the disease causing of a family with hereditary spastic paraplegia. Methods: Detailed clinical characterization analysis was undertake in the HSP family, taking peripheral blood sample from the 9 subjects for the extraction of genomic DNA and the proband underwent next generation sequencing. Potentially causative variants were identified by Sanger sequencing and multiplex ligation-dependent probe amplification. Results: In this study, we obtained clinical and genetic findings in the family with HSP. There were four generations including 47 members, and ten affected members displayed pure HSP, they showed clinical phenotyping that varied in their severity. Gene sequencing suggested that the proband has carried a novel heterozygous variant c.1057_1058insCC in the SPAST gene, and the same mutation was identified in other affected family members.Conclusions: Here, we showed a family with pure autosomal dominant HSP type 4(SPG4). The novel mutation c.1057_1058insCC of SPAST is the causative variant in this HSP-SPG4 family. And the persent study expands the mutation spectrum of SPAST and provides an opportunity to study the genotype-phenotype correlation in SPG4.

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The investigation of genetic and clinical features in patients with hereditary spastic paraplegia in central‐Southern China

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 7 publications

References 28 publications

Hereditary Spastic Paraplegia: An Update

Hereditary Spastic Paraplegia: An Update

Clinical features and genetic spectrum of Chinese patients with hereditary spastic paraplegia: A 14-year study

A SPAST gene-related hereditary spastic paraplegia type 4 family: Identification by a novel mutation

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