Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia
Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia
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DOI：
10.1007/pl00007865
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发表时间：
2002-02-01
影响因子：
6
通讯作者：
Santorelli, FM
中科院分区：
文献类型：
--
作者：
Patrono, C;Casali, C;Santorelli, FM
我们研究了9个意大利家庭与纯形式的常染色体显性遗传性痉挛性截瘫（ADHSP），以评估SPG 4基因突变的频率。我们观察到发病年龄和临床严重程度的明显家族内变异，从严重的先天性表现到55岁后的轻度受累，再到70岁后的突变健康携带者。9个先证者中有4个携带SPG 4突变，我们发现了3个新的SPG 4突变，所有突变都预示着功能丧失，对痉挛素功能有明显的重要影响。RT-PCR研究预测功能丧失是导致spastin相关HSP的可能机制。目前的研究扩大了SPG 4中等位基因变体的谱，证实了它们在纯AD-HSP中的病理意义，并暗示了spastin的假定功能。
We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-function with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin.