Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia
Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia
复制标题
DOI：
10.1038/15472
复制
发表时间：
1999-11-01
期刊：
影响因子：
30.8
通讯作者：
Weissenbach, J
中科院分区：
文献类型：
--
作者：
Hazan, J;Fonknechten, N;Weissenbach, J
常染色体显性遗传性痉挛截瘫(AD-HSP)是一种以进行性肢体痉挛为特征的遗传性异质性神经退行性疾病。在迄今发现的4个AD-HSP基因座中，位于染色体2p21-p22的SPG4基因座占所有AD-HSP家系的40-50%。利用基于获得SPG4全序列的定位克隆策略，我们鉴定了一个编码AAA蛋白家族新成员的候选基因，我们将其命名为spastin。对7个SPG4连锁家系的该基因进行了序列分析，发现了几种DNA修饰，包括错义、无义和剪接点突变。SPG4及其小鼠同源基因在胎儿和成人组织中早期和普遍表达。序列同源性和推测的亚细胞定位表明，该ATPase参与了核蛋白复合体的组装或功能。
Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a genetically heterogeneous neurodegenerative disorder characterized by progressive spasticity of the lower limbs. Among the four loci causing AD-HSP identified so far, the SPG4 locus at chromosome 2p21-p22 has been shown to account for 40-50% of all AD-HSP families. Using a positional cloning strategy based on obtaining sequence of the entire SPG4 interval, we identified a candidate gene encoding a new member of the AAA protein family, which we named spastin. Sequence analysis of this gene in seven SPG4-linked pedigrees revealed several DNA modifications, including missense, nonsense and splice-site mutations. Both SPG4 and its mouse orthologue were shown to be expressed early and ubiquitously in fetal and adult tissues. The sequence homologies and putative subcellular localization of spastin suggest that this ATPase is involved in the assembly or function of nuclear protein complexes.