Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower limbs. HSP is caused by failure of development or selective degeneration of the corticospinal tracts, which contain the longest axons in humans. The most common form of HSP is caused by mutations of the spastin gene (SPAST), located on chromosome 2p21-p22, which encodes spastin, one of the ATPases associated with diverse cellular activities (AAA). In this study, we detected four causative mutations of SPAST among 14 unrelated patients with spastic paraplegia. Two missense mutations (1447A-->G, 1207C-->G) and two deletion mutations (1465delT, 1475-1476delAA) were located in the AAA cassette region. Three of these four mutations were novel. Previous reports and our results suggest that the frequency of SPAST mutations is higher among Japanese patients with autosomal dominant HSP, although SPAST mutations are also observed in patients with sporadic spastic paraplegia.

中文翻译：

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在患有痉挛性截瘫的日本家庭中，spastin基因的四个突变。

遗传性痉挛性截瘫（HSP）是一组遗传性异质性神经退行性疾病，其特征是缓慢进行性痉挛和下肢无力。HSP是由皮质脊髓束的发育或选择性变性失败引起的，而皮质脊髓束含有人类最长的轴突。HSP最常见的形式是由位于2p21-p22染色体上的spastin基因（SPAST）突变引起的，该基因编码spastin，spastin是与多种细胞活性（AAA）相关的ATPase之一。在这项研究中，我们在14例无关的痉挛性截瘫患者中检测到4种SPAST致病突变。两个错义突变（1447A-> G，1207C-> G）和两个缺失突变（1465delT，1475-1476delAA）位于AAA盒区域。这四个突变中的三个是新颖的。