期刊
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
卷 15, 期 7-8, 页码 557-562出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/21678421.2014.920033
关键词
Amyotrophic lateral sclerosis; fused in sarcoma; truncation
资金
- Patrick Berthoud Charitable Trust
- MND Association
- MRC [G0900635, G1100695, G0600974, G0500289, G0501573, MC_G1000733, G0900688] Funding Source: UKRI
- Medical Research Council [G0900688, MC_G1000733, G0600974, G1100695, MR/L501529/1, G0501573, G0500289B, G0900635, G0500289] Funding Source: researchfish
- Motor Neurone Disease Association [Talbot/Apr11/811-791] Funding Source: researchfish
Mutations in the gene encoding the RNA-binding protein fused in sarcoma (FUS) account for 4 - 5% of familial cases of amyotrophic lateral sclerosis (ALS). We describe the identification and in vitro cellular characterization of a genetic mutation in a family in which the index case, and subsequently her two children, each developed rapidly progressive ALS at a young age and died within a year of onset. Exome capture and sequencing revealed a mutation in the FUS gene consisting of a 2-bp deletion, c.1509_1510delAG, resulting in a predicted truncated protein, p.G504Wfs*12, lacking the nuclear localization signal. Expression of this mutation in HEK293 and NSC-34 cells demonstrated severe cytoplasmic mislocalization of mutant FUS, and colocalization with stress granules when compared to wild-type, R521C and P525L mutant FUS. This study provides further evidence of a broad correlation between clinical severity of FUS-related ALS and mislocalization of the protein to the cytoplasm.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据