Phenotype of AD-HSP due to mutations in the SPAST gene
Phenotype of AD-HSP due to mutations in the SPAST gene
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SPAST 基因突变导致的 AD-HSP 表型
作者：
P. Mcmonagle;P. Byrne;B. Fitzgerald;S. Webb;Nollaig A. Parfrey;Michael Hutchinson
背景：单纯性常染色体显性遗传性痉挛性轻瘫（AD HSP）在临床和遗传上具有异质性。至少有7个遗传位点，发病和残疾年龄各不相同。位于染色体2 p上SPG 4位点的SPAST基因是AD-HSP的主要致病基因。目的：研究SPAST基因突变导致的AD-HSP家系与排除SPG 4基因突变的AD-HSP家系相比，是否有不同的临床特征。方法：确定19个“纯”AD-HSP家系，采用标准方案比较家系成员的临床特征。利用遗传学研究，将这些家庭分为两组进行比较：SPAST突变的家庭，“突变阳性”组，以及根据连锁研究排除SPG 4的家庭，“SPG 4排除”组。结果如下：来自4个家庭的29个个体有SPAST突变，而来自3个家庭的22个个体组成了SPG 4排除组;在11个家庭中，连锁模式未知。在剩下的一个家族中，尽管与SPG 4有很强的联系，但没有发现突变。在四个SPAST家系中发现了不同的突变，但每个家系的临床表现相似。突变阳性组与SPG 4排除组的比较显示，在SPAST突变的受影响个体中，发病年龄更大（p = 0.03），残疾更多（p = 0.001），进行性轻瘫更快（p = 0.044），认知障碍更多（p = 0.024），不受疾病持续时间的混淆。结论：尽管突变不同，但SPAST家族具有相似的表型，可以与其他遗传群体区分开来。
Background: “Pure” autosomal dominant hereditary spastic paraparesis (AD-HSP) is clinically and genetically heterogeneous. There are at least seven genetic loci with varying ages at onset and disability. The SPAST gene at the SPG4 locus on chromosome 2p is the major disease gene for AD-HSP. Objectives: To investigate whether there are distinct clinical features among families with AD-HSP due to SPAST mutations compared with families excluded from SPG4. Methods: Nineteen families with “pure” AD-HSP were identified, and the clinical features of family members were compared using a standard protocol. With use of genetic studies, the families were divided into two groups for comparison: those with mutations in SPAST, the “mutation-positive” group, and those excluded from SPG4 on the basis of linkage studies, the “SPG4-excluded” group. Results: Twenty-nine individuals from four families had mutations in SPAST, whereas 22 individuals from three families comprised the SPG4-excluded group; in 11 families, the pattern of linkage was unknown. In the one remaining family, no mutations were found despite strong linkage to SPG4. Different mutations were identified in the four SPAST pedigrees, but the clinical picture was similar in each. Comparison of the mutation-positive group with the SPG4-excluded group revealed an older age at onset (p = 0.03), more disability (p = 0.001), more rapidly progressive paraparesis (p = 0.044), and more cognitive impairment (p = 0.024) among affected individuals with SPAST mutations, not confounded by disease duration. Conclusion: Despite different mutations, SPAST families have a similar phenotype that can be distinguished from other genetic groups.
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影响因子：
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