Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6.
Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6.
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DOI：
10.1126/science.1165942
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发表时间：
2009-02-27
期刊：
影响因子：
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通讯作者：
Shaw CE
中科院分区：
文献类型：
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作者：
Vance C;Rogelj B;Hortobágyi T;De Vos KJ;Nishimura AL;Sreedharan J;Hu X;Smith B;Ruddy D;Wright P;Ganesalingam J;Williams KL;Tripathi V;Al-Saraj S;Al-Chalabi A;Leigh PN;Blair IP;Nicholson G;de Belleroche J;Gallo JM;Miller CC;Shaw CE
肌萎缩性侧索硬化症（ALS）是一种致命的神经退行性疾病，10%的病例是家族性的。我们已经确定了一个错义突变的基因编码融合在肉瘤（FUS）在英国亲属，与ALS6。在对197例家族性ALS指数病例的调查中，我们在8个家族中发现了另外两个错义突变。三例FUS突变病例的尸检分析显示FUS免疫反应性细胞质包涵体和主要的低运动神经元变性。细胞表达研究显示突变的FUS蛋白异常定位。FUS参与转录、RNA剪接和转运的调控，它与另一个ALS基因TARDBP具有功能同源性，这表明运动神经元变性可能存在共同的机制。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is familial in 10% of cases. We have identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6. In a survey of 197 familial ALS index cases, we identified two further missense mutations in eight families. Postmortem analysis of three cases with FUS mutations showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.