SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia
SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia
复制标题
DOI：
10.1212/01.wnl.0000294327.66106.3d
复制
发表时间：
2008-04-15
期刊：
影响因子：
9.9
通讯作者：
Singleton, A.
中科院分区：
文献类型：
--
作者：
Paisan-Ruiz, C.;Dogu, O.;Singleton, A.
工作背景：常染色体隐性遗传性痉挛性截瘫（ARHSP）伴胼胝体薄（TCC）是复杂性遗传性痉挛性截瘫的一种常见形式。ARHSP-TCC的遗传病变定位于染色体15 q13-q15，命名为SPG 11。最近，编码spatacsin的基因方法：我们对25例散发性或家族性ARHSP-TCC患者的40个编码外显子进行了完整的分析。（20名先证者）复杂遗传性痉挛性截瘫伴和不伴胼胝体变薄。我们鉴定了七个突变，包括缺失、插入和无义突变，这些突变都被预测会导致蛋白质的过早截短。我们的结论是KIAA 1840突变在复杂的常染色体隐性遗传性痉挛性截瘫中是常见的，但在散发的复杂遗传性痉挛性截瘫中是罕见的。痉挛性截瘫
Background: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common form of complex hereditary spastic paraplegia. The genetic lesion underlying ARHSP-TCC was localized to chromosome 15q13-q15 and given the designation SPG11. Recently, the gene encoding spatacsin (KIAA1840) has been shown to contain mutations that underlie the majority of ARHSP-TCC cases.Methods: We present a complete analysis of the 40 coding exons of this gene in patients with sporadic (n = 25) or familial (20 probands) complex hereditary spastic paraplegia with and without thinning of the corpus callosum.Results: We identified seven mutations, including deletions, insertions, and nonsense mutations, which were all predicted to lead to premature truncation of the protein.Conclusion: We conclude that mutations on KIAA1840 are frequent in complex autosomal recessive hereditary spastic paraplegia but an infrequent cause of sporadic complex hereditary spastic paraplegia.