期刊
EUROPEAN JOURNAL OF HUMAN GENETICS
卷 18, 期 1, 页码 130-132出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2009.122
关键词
Stuve-Wiedemann Syndrome; premature termination codon readthrough; gentamycin; lethal condition
资金
- 'Association Francaise contre les Myopathies' (AFM) [N 12811, N 12807]
The Stuve-Wiedemann Syndrome (SWS) is a frequently lethal chondrodysplasia caused by null mutations in the leukemia inhibitory factor receptor gene (LIFR) responsible for an impaired activation of the JAK-STAT pathway after LIF stimulation. Most LIFR mutations are nonsense mutations, thus prompting us to investigate the impact of aminoglycosides on the readthrough of premature termination codons (PTCs). Culturing skin fibroblasts from three SWS patients and controls for 48 h in the presence of gentamycin (200-500 mu g/ml) partially restored the JAK-STAT3 pathway when stimulated by LIF. Consistently, quantitative RT-PCR analysis showed that gentamycin stabilized LIFR mRNAs carrying UGA premature termination codons. We conclude that high gentamycin concentrations can partially restore functional LIFR protein synthesis in vitro, prompting us to investigate PTC readthrough using less toxic and more efficient drugs in this presently untreatable lethal condition. European Journal of Human Genetics (2010) 18, 130-132; doi:10.1038/ejhg.2009.122; published online 15 July 2009
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