Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis
Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis
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DOI：
10.1136/jmg.37.10.759
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发表时间：
2000-10-01
影响因子：
4
通讯作者：
Bushby, KMD
中科院分区：
文献类型：
--
作者：
Lindsey, JC;Lusher, ME;Bushby, KMD
背景-遗传性痉挛性截瘫是一种遗传异质性疾病。目的：研究遗传性痉挛截瘫患者中染色体2p21-22上spastin基因(SPG4)的突变。方法采用单链构象多态分析和测序的方法，对32例患者(其中12例来自已知的SPG4连锁家系)进行spastin基因突变分析。结果：共鉴定出13个SPG4突变，其中11个为新发现。这些突变包括错义突变、无义突变、移码突变和剪接位点突变，其中大部分会影响AAA盒。我们还描述了这个保守区域之外的核苷酸替换，似乎表现为隐性突变。结论-spastin基因的反复突变是罕见的。这降低了作为遗传性痉挛截瘫患者诊断工作的一部分的突变检测的简易性。我们的发现对推测spastin的功能和HSP患者的突变检测方案具有重要的意义。
Background-Hereditary spastic paraparesis is a genetically heterogeneous condition. Recently, mutations in the spastin gene were reported in families Linked to the common SPG4 locus on chromosome 2p21-22.Objectives-To study a population of patients with hereditary spastic paraparesis for mutations in the spastin gene (SPG4) on chromosome 2p21-22.Methods-DNA from 32 patients (12 from families known to be linked to SPG4) was analysed for mutations in the spastin gene by single strand conformational polymorphism analysis and sequencing. All patients were also examined clinically.Results-Thirteen SPG4 mutations were identified, 11 of which are novel. These mutations include missense, nonsense, frameshift, and splice site mutations, the majority of which affect the AAA cassette. We also describe a nucleotide substitution outside this conserved region which appears to behave as a recessive mutation.Conclusions-Recurrent mutations in the spastin gene are uncommon. This reduces the ease of mutation detection as a part of the diagnostic work up of patients with hereditary spastic paraparesis. Our findings have important implications for the presumed function of spastin and schemes for mutation detection in HSP patients.