Abstract：
Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative disorders, which is characterized by the presence of progressive spasticity and weakness in bilateral lower limbs. Spastic paraplegia 62 (SPG62) caused by the endoplasmic reticulum lipid raft associated 1 (ERLIN1) gene mutation is a rare subtype of HSP. Herein, we report the case of the first Chinese SPG62 patient, explore the potential pathogenic mechanism and review ERLIN1-related HSP patients. A 23-year-old man had progressive difficulty in walking and gait abnormalities for more than 11 years. Physical examination showed slightly reduced muscle strength (5-/5) and elevated muscle tone in the lower limbs and hyperreflexia in four limbs. Genetic analysis identified a novel splicing site mutation in ERLIN1 gene (c.504+1G > A), which was predicted to disturb the normal splicing process of mRNA by bioinformatic tools. Minigene experiment further confirmed the mutation c.504+1G > A could cause erroneous deletion of Exon 7 in the mRNA, which may change the conserved prohibitin (PHB) domain of erlin-1 and affect the function of erlin1/2 complex. Thus, we identified a pathogenic mutation of ERLIN1 splicing site causing delayed-onset pure HSP. This study widened the genetic and phenotypic spectrum of SPG62.
摘要：
遗传性痉挛性截瘫（HSP）是一组遗传性神经退行性疾病，其特征在于双侧下肢存在进行性痉挛和无力。由内质网脂筏相关1(ERLIN1)基因突变引起的痉挛性截瘫62(SPG62)是HSP的一种罕见亚型。在这里，我们报道了首例中国SPG62患者，探讨可能的致病机制,并对ERLIN1相关HSP患者进行综述。一名23岁的男子在行走和步态异常方面有进行性困难超过11年。体格检查显示下肢肌肉力量（5-/5）略有降低，肌肉张力升高，四肢反射亢进。遗传分析在ERLIN1基因中发现了一个新的剪接位点突变（c.504+1G>A），生物信息学工具预测这会干扰mRNA的正常剪接过程。Minigene实验进一步证实突变c.504+1G>A可能导致mRNA中外显子7的错误缺失，这可能会改变erlin-1的保守抑制素（PHB）结构域并影响erlin1/2复合物的功能。因此，我们确定了一个引起延迟发作的纯HSP的ERLIN1剪接位点的致病突变。本研讨拓宽了SPG62的遗传和表型谱。
