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
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Parkinsonism Relat Disord. 2021 Jun;87:87-91. doi: 10.1016/j.parkreldis.2021.05.004. Epub 2021 May 11.
To investigate the clinical and genetic features of hereditary spastic paraplegia (HSP) type 3A (SPG3A) in Taiwan.
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.
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.
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.
研究台湾地区3A型遗传性痉挛性截瘫（HSP，即SPG3A）的临床及遗传学特征。
对274名无血缘关系的台湾HSP患者进行ATL1基因的突变分析。通过ATL1基因中存在杂合致病性突变来确诊SPG3A。对SPG3A患者进行临床、电生理及神经影像学评估。使用痉挛性截瘫评定量表（SPRS）和残疾评分评估疾病严重程度。对ATL1侧翼的19个单核苷酸多态性（SNP）标记进行基因分型，以对ATL1 p.R416C突变进行单倍型分析。
鉴定出11个家系中的18名SPG3A患者。他们通常表现为纯合型HSP表型，发病年龄在1至68岁之间。鉴定出5种杂合的ATL1突变，包括p.R239C、p.V253I、p.Y336H、p.P342R和p.R416C。ATL1 p.R416C是最常见的突变，出现在5个SPG3A家系中。单倍型分析显示，在携带p.R416C等位基因的12名个体中存在共享单倍型。
在台湾队列中，SPG3A占HSP的4%（274例中的11例）。台湾携带ATL1 p.R416C突变的患者可能源自共同祖先。本研究明确了台湾地区SPG3A的临床及遗传学特征，为诊断和管理提供了有用信息，尤其是对汉族血统的患者。
