Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis
Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis
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DOI：
10.1126/science.1166066
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发表时间：
2009-02-27
期刊：
影响因子：
56.9
通讯作者：
Brown, R. H., Jr.
中科院分区：
文献类型：
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作者：
Kwiatkowski, T. J., Jr.;Bosco, D. A.;Brown, R. H., Jr.
肌萎缩性侧性硬化症（ALS）是致命的退化运动神经元疾病。十个案件是继承的；大多数涉及身份不明的基因。我们在这里报告了肉瘤中融合的13个突变/在脂肪肉瘤（FUS/TLS）基因16染色体上的转换，该突变是家族性ALS的特定的。 FUS/TLS蛋白与RNA结合，在各种过程中起作用，通常位于细胞核中。相反，FUS/TLS的突变形式积累在神经元的细胞质中，这种病理与基因TAR DNA结合蛋白43（TDP43）相似，其突变也会引起ALS。因此，神经元细胞质蛋白聚集和RNA代谢缺陷似乎是ALS及其其他神经退行性疾病中涉及的常见致病机制。
Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.