Li Rui, Liu Xuan, Ke Chenming, Zeng Fanli, Zeng Qingyi, Xu Xiaowei, Fan Xiaoqin, Zhang Ying, Hou Qinghua
Department of Neurology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China.
Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
Front Neurol. 2024 Jul 1;15:1365787. doi: 10.3389/fneur.2024.1365787. eCollection 2024.
Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disease prominently characterized by slowly progressive lower limb weakness and spasticity. The significant genotypic and phenotypic heterogeneity of this disease makes its accurate diagnosis challenging. In this study, we identified the NM_001168272: c.2714A > G (chr3.hg19: g.4716912A > G, N905S) variant in the gene in a three-generation Chinese family with multiple individuals affected by HSP, which we believed to be associated with HSP pathogenesis. To confirm, we performed whole exome sequencing, copy number variant assays, dynamic mutation analysis of the entire family, and protein structure prediction. The variant identified in this study was in the coupling domain, and this is the first corroborated report assigning ITPR1 variants to HSP. These findings expand the clinical and genetic spectrum of HSP and provide important data for its genetic analysis and diagnosis.
遗传性痉挛性截瘫（HSP）是一种罕见的神经退行性疾病，其主要特征为下肢进行性肌无力和痉挛。该疾病显著的基因型和表型异质性使其准确诊断具有挑战性。在本研究中，我们在一个三代均有多人患HSP的中国家系中，于 基因中鉴定出NM_001168272: c.2714A > G（chr3.hg19: g.4716912A > G，N905S）变异，我们认为该变异与HSP发病机制相关。为进行确认，我们开展了全外显子组测序、拷贝数变异分析、对整个家系的动态突变分析以及蛋白质结构预测。本研究中鉴定出的变异位于偶联结构域，这是首份将ITPR1变异与HSP相关联的经证实报告。这些发现拓宽了HSP的临床和遗传谱，为其遗传分析和诊断提供了重要数据。
