Clinical characteristics of Taiwanese patients with Hereditary spastic paraplegia type 5
Clinical characteristics of Taiwanese patients with Hereditary spastic paraplegia type 5
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DOI：
10.1002/acn3.51019
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发表时间：
2020-03-22
影响因子：
5.3
通讯作者：
Lee, Yi-Chung
中科院分区：
文献类型：
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作者：
Chou, Cheng-Ta;Soong, Bing-Wen;Lee, Yi-Chung
目的探讨台湾地区SPG5的临床、电生理、神经影像学特征及遗传特征。方法对187例台湾无亲缘关系HSP患者进行CYP7B1编码区突变分析。SPG5的诊断是通过存在双等位基因CYP7B1突变来确定的。SPG5患者接受临床、电生理和神经影像学评估。采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CYP7B1侧的2个微卫星标记和18个单核苷酸多态性（SNP）标记进行基因分型，评估CYP7B1 p.R112*突变的奠基者效应。结果19例SPG5患者来自17个家庭。他们通常在8至40岁开始出现伴有本体感觉受累的进行性痉挛性截瘫。他们的mri常显示双侧枕顶区白质异常、脊髓萎缩和轻度小脑萎缩。在CYP7B1中发现了6个不同的突变，包括3个新突变（p.N131Ifs*4、p.A295V和p.L439R）。CYP7B1 p.R112*是最常见的突变，在17个SPG5家系中占88.2%。纯合子CYP7B1 p.R112*突变患者的临床严重程度较轻。详细的单倍型分析表明，在25个携带至少一个CYP7B1 p.R112*等位基因的个体中存在一个共享的单倍型，这表明存在奠基者效应。本研究描述了SPG5在台湾独特的临床和遗传特征，为SPG5的诊断和治疗提供了有用的信息，特别是在中国血统的患者中。
Objectives To investigate the clinical, electrophysiological, neuroimaging characteristics and genetic features of SPG5 in Taiwan.Methods Mutational analysis of the coding regions of CYP7B1 was performed by utilizing targeted resequencing analysis of the 187 unrelated Taiwanese HSP patients. The diagnosis of SPG5 was ascertained by the presence of biallelic CYP7B1 mutations. The SPG5 patients received clinical, electrophysiological, and neuroimaging evaluations. Disease severity was assessed by using the Spastic Paraplegia Rating Scale (SPRS) and the disability score. Two microsatellite markers as well as 18 single-nucleotide polymorphism (SNP) markers flanking CYP7B1 were genotyped to assess the founder effect of the CYP7B1 p.R112* mutation.Results Nineteen SPG5 patients from 17 families were identified. They typically presented an insidious onset progressive spastic paraparesis with proprioception involvement beginning at age 8 to 40 years. Their MRIs often showed white matter abnormalities in bilateral occipito-parietal regions, spinal cord atrophy, and mild cerebellar atrophy. Six different mutations in CYP7B1 were recognized, including three novel ones (p.N131Ifs*4, p.A295V, and p.L439R). CYP7B1 p.R112* was the most common mutation and present in 88.2% of the 17 SPG5 pedigrees. The patients with homozygous CYP7B1 p.R112* mutations had a milder clinical severity. Detailed haplotype analyses demonstrated a shared haplotype in the 25 individuals carrying at least one single allele of CYP7B1 p.R112*, suggesting a founder effect.Interpretation This study delineates the distinct clinical and genetic features of SPG5 in Taiwan and provides useful information for the diagnosis and management of SPG5, especially in patients of Chinese descent.