Ki Chang-Seok, Lee Won Yong, Han Do Hoon, Sung Duk Hyun, Lee Kyung-Bok, Lee Kyung-A, Cho Sang Seon, Cho Seunghee, Hwang Hyokkee, Sohn Kwang Min, Choi Yeun Joo, Kim Jong-Won
Department of Clinical Pathology, Sungkyunkwan University School of Medicine, Samsung Medical Center, #50 Ilwon-Dong, Kangnam-Gu, Seoul 135-710, Korea.
J Hum Genet. 2002;47(9):473-7. doi: 10.1007/s100380200068.
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.
遗传性痉挛性截瘫（HSP）是一组临床和遗传异质性神经退行性疾病，其特征为下肢进行性痉挛和无力。在与常染色体显性（AD）-HSP相关的8个基因座中，位于2号染色体2p22的SPG4基因座约占所有患者的40%。最近，一种名为spastin的AAA蛋白家族新成员中的突变已被确定为与SPG4相关的AD-HSP的病因。在此，我们描述了在一个具有典型纯AD-HSP临床特征的韩国家庭中，在SPG4基因第7外显子中发现的一种新的错义突变（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因错义突变而改变的结构域中最靠前的部分。携带I344K突变的受影响个体的临床表现与先前报道的具有SPG4突变的纯AD-HSP患者并无不同。然而，值得注意的是，该家族中未发现排尿功能障碍和上肢受累情况。据我们所知，这是韩国首例经基因证实的AD-HSP报告。
