Mutation analysis of the TIA1 gene in Chinese patients with amyotrophic lateral sclerosis and frontotemporal dementia
Mutation analysis of the TIA1 gene in Chinese patients with amyotrophic lateral sclerosis and frontotemporal dementia
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DOI：
10.1016/j.neurobiolaging.2017.12.017
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发表时间：
2017-12
影响因子：
4.2
通讯作者：
Zhenhua Yuan;Bin Jiao;Li-li Hou;Tingting Xiao;Xi-xi Liu;Junling Wang;Jun Xu;Lin Zhou;Xinxiang Yan;B. Tang;Lu Shen
中科院分区：
文献类型：
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作者：
Zhenhua Yuan;Bin Jiao;Li-li Hou;Tingting Xiao;Xi-xi Liu;Junling Wang;Jun Xu;Lin Zhou;Xinxiang Yan;B. Tang;Lu Shen
肌萎缩侧索硬化症(ALS)是一种以大脑和脊髓运动神经元进行性丧失为特征的致死性神经退行性疾病。额颞性痴呆(FTD)是一组以行为进行性恶化、执行功能障碍和言语障碍为特征的痴呆综合征。越来越多的证据表明，这两种疾病具有共同的遗传病因和病理生理机制。最近，在高加索人ALS和ALS-FTD患者中发现了RNA结合蛋白T细胞限制性胞内抗原1(TIA1)基因低复杂区域的罕见突变。然而，TIA1基因在中国ALS和FTD患者中还没有进行全面的突变分析。在这项研究中，我们在大陆中国的241名ALS和51名FTD患者中筛选出TIA1的低复杂性区域。结果在2例散发性ALS患者中发现了2个新的错义突变(p.P352L和p.I300T)，而在FTD患者中未发现突变。据我们所知，这份报告首次在中国人群中对ALS和FTD患者的TIA1基因进行了突变分析。我们的发现拓宽了ALS患者的已知突变谱，并进一步证实了TIA1是ALS的一个新的致病基因。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. Frontotemporal dementia (FTD) is a group of dementia syndromes characterized by the progressive deterioration of behaviors, executive dysfunction, and verbal impairment. Increasing evidence indicates that these 2 diseases share a common genetic etiology and pathophysiological mechanism. Recently, rare mutations in the low-complexity domain of the RNA-binding protein T-cell–restricted intracellular antigen-1 (TIA1) gene were identified in Caucasian ALS and ALS-FTD patients. However, no comprehensive mutation analysis of theTIA1gene has been performed in Chinese patients with ALS and FTD. In this study, we screened the low-complexity domain ofTIA1in a cohort of 241 ALS and 51 FTD patients in mainland China. As a result, 2 novel missense mutations (p.P352L and p.I300T) were identified in 2 sporadic patients with ALS, while no mutation was found in FTD cases. To the best of our knowledge, this report presented the first mutation analysis of theTIA1gene in patients with ALS and FTD in Chinese population. Our findings broaden the known mutational spectrum in patients with ALS and further confirmTIA1as a novel causative gene of ALS.