Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China.
Mol Med Rep. 2023 Apr;27(4). doi: 10.3892/mmr.2023.12966. Epub 2023 Feb 24.
Hereditary spastic paraplegia (HSP) comprises a group of hereditary and neurodegenerative diseases that are characterized by axonal degeneration or demyelination of bilateral corticospinal tracts in the spinal cord; affected patients exhibit progressive spasticity and weakness in the lower limbs. The most common manifestation of HSP is spastic paraplegia type 4 (SPG4), which is caused by mutations in the spastin () gene. The present study reports the clinical characteristics of affected individuals and sequencing analysis of a mutation that caused SPG4 in a family. All affected family members exhibited spasticity and weakness of the lower limbs and, notably, only male members of the family were affected. Whole‑exome sequencing revealed that all affected individuals had a novel c.1785C>A (p. Ser595Arg) missense mutation in . Bioinformatics analysis revealed changes in both secondary and tertiary structures of the mutated protein. The novel missense mutation in supported the diagnosis of SPG4 in this family and expands the spectrum of pathogenic mutations that cause SPG4. Analysis of sequences revealed that most pathogenic mutations occurred in the AAA domain of the protein, which may have a close relationship with SPG4 pathogenesis.
遗传性痉挛性截瘫（HSP）是一组遗传性和神经退行性疾病，其特征是脊髓双侧皮质脊髓束轴突变性或脱髓鞘；受影响的患者表现为下肢进行性痉挛和无力。HSP 最常见的表现形式是痉挛性截瘫 4 型（SPG4），由 spastin（）基因突变引起。本研究报告了一个家系中 SPG4 相关突变的临床特征和测序分析。所有受影响的家族成员均表现出下肢痉挛和无力，值得注意的是，只有家族中的男性成员受到影响。全外显子组测序显示，所有受影响的个体均存在 的新型 c.1785C>A（p.Ser595Arg）错义突变。生物信息学分析显示突变蛋白的二级和三级结构均发生变化。该家系中 的新型错义突变支持 SPG4 的诊断，并扩展了导致 SPG4 的致病性突变谱。对 序列的分析表明，大多数致病性突变发生在蛋白的 AAA 结构域，这可能与 SPG4 的发病机制密切相关。
