A novel variant (p.A524P) in Spastin is responsible for a Chinese family with hereditary spastic paraplegia.

Autor: Jin YH; Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, 410013, China., Xiang YZ; Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, 410013, China., Zhao MF; Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, 410013, China., Liu YH; Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou, 225001, China., Fan LL; Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, 410013, China. swfanliangliang@csu.edu.cn., Li XC; Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou, 225001, China. leeshawnc@outlook.com.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2024 Sep 04; Vol. 51 (1), pp. 951. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1007/s11033-024-09880-0
Abstrakt: Background: Hereditary spastic paraplegia (HSP) represents a group of monogenic neurodegenerative disorders characterized by high clinical and genetic heterogeneity. HSP is characterized by slowly progressing hypertonia of both lower extremities, spastic gait, and myasthenia. The most prevalent autosomal dominant form of HSP, known as spastic paraplegia 4 (SPG4), is attributed to variants in the spastin (SPAST) gene.
Methods and Results: Here, a Chinese family presenting with spasticity in both legs and a shuffling gait participated in our investigation. Whole exome sequencing of the proband was utilized to identify the genetic lesion in the family. Through data filtering, Sanger sequencing validation, and co-separation analysis, a novel variant (NM_014946.3: c.1669G > C:p.A557P) of SPAST was identified as the genetic lesion of this family. Furthermore, bioinformatic analysis revealed that this variant was deleterious and located in a highly evolutionarily conserved site.
Conclusion: Our study confirmed the diagnosis of SPG4 in this family, contributing to genetic counseling for families affected by SPG4. Additionally, our study broadened the spectrum of SPAST variants and highlighted the importance of ATPases associated with various cellular activity domains of SPAST.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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