Clinical and genetic characterization of hereditary spastic paraplegia type 3A in Taiwan. (June 2021)

• Record Type: Journal Article
• Authors: Hsu, Shao-Lun; Hsueh, Hsueh-Wen; Chen, Shih-Ying; Chang, Yung-Yee; Tan, Shennie; Hong, Chien-Tai; Tsai, Yu-Shuen; Yu, Kai-Wei; Wu, Hsiu-Mei; Liao, Yi-Chu; Soong, Bing-Wen; Hu, Chaur-Jong; Lan, Min-Yu; Lee, Yi-Chung
• Is Part Of: Parkinsonism & related disorders. Volume 87(2021)
• Page Start: 87
• Page End: 91
• Publication Date: 2021-06
• Subjects: Hereditary spastic paraplegia -- HSP -- SPG3A -- ATL1 -- Atlastin-1; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2021.05.004
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Aim: To investigate the clinical and genetic features of hereditary spastic paraplegia (HSP) type 3A (SPG3A) in Taiwan. Methods: Mutational analysis of the ATL1 gene was performed for 274 unrelated Taiwanese HSP patients. The diagnosis of SPG3A was ascertained by the presence of a heterozygous pathogenic mutation in ATL1 . The SPG3A patients received clinical, electrophysiological, and neuroimaging evaluations. Disease severity was assessed by using Spastic Paraplegia Rating Scale (SPRS) and disability score. Nineteen single nucleotide polymorphism (SNP) markers flanking ATL1 were genotyped for haplotype analysis of ATL1 p.R416C mutation. Results: Eighteen SPG3A patients from 11 families were identified. They typically presented a pure form HSP phenotype with disease onset ranging from age 1–68 years. Five heterozygous ATL1 mutations were identified, including p.R239C, p.V253I, p.Y336H, p.P342R and p.R416C. ATL1 p.R416C was the most common mutation and presented in five SPG3A pedigrees. Haplotype analyses demonstrated a shared haplotype in the 12 individuals carrying a p.R416C allele. Conclusion: SPG3A accounts for 4% (11 out of 274) of HSP in the Taiwanese cohort. Patents with the ATL1 p.R416C mutation in Taiwan may descend from a common ancestor. This study defines the clinical and genetic features of SPG3A in Taiwan and provides useful information for the diagnosis and management, especially in patients of Han Chinese descent. Highlights: Five different ATL1 mutations were identified in 11 Taiwanese SPG3A families. The SPG3A patients typically manifest with pure HSP starting from age 1–68 years. The ATL1 p.P342R is a novel mutation for SPG3A. There is a founder effect for ATL1 p.R416C in Taiwan.