Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower extremities. Among eight loci linked with autosomal-dominant (AD)-HSP, the SPG4 locus on chromosome 2p22 accounts for about 40% of all patients. Recently, mutations in a new member of the AAA protein family, called spastin, have been identified as responsible for SPG4-linked AD-HSP. Here, we describe a novel missense mutation (c.1031T>A; I344K) in exon 7 of the SPG4 gene identified in a Korean family with typical clinical features of pure AD-HSP. The mutation affects the third amino acid of the highly conserved AAA cassette domain, which is the most fore part of the domain altered by a missense mutation reported so far. Clinical presentations of affected individuals carrying the I344K mutation were not different from those of pure AD-HSP with SPG4 mutations reported previously. However, it is noteworthy that neither urinary dysfunction nor involvement of upper extremities was noticed in this family. To our knowledge, this is the first report of genetically confirmed AD-HSP in Korea.

中文翻译：

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韩国家庭常染色体显性遗传性痉挛性截瘫的SPG4基因中的新型错义突变（I344K）。

遗传性痉挛性截瘫（HSP）是一组临床和遗传上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。在与常染色体显性（AD）-HSP相关的八个基因座中，染色体2p22上的SPG4基因座约占所有患者的40％。最近，已确定AAA蛋白家族中一个称为spastin的新成员中的突变是SPG4连接的AD-HSP的原因。在这里，我们描述了在韩国家庭中发现的具有纯AD-HSP典型临床特征的SPG4基因第7外显子中的新型错义突变（c.1031T> A； I344K）。该突变影响高度保守的AAA盒结构域的第三个氨基酸，这是迄今为止报道的错义突变所改变的结构域的最重要部分。携带I344K突变的受影响个体的临床表现与先前报道的带有SPG4突变的纯AD-HSP的临床表现无差异。但是，值得注意的是，这个家庭既没有发现泌尿功能障碍也没有上肢受累。据我们所知，这是韩国首次通过基因证实的AD-HSP报告。