Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China.
Neurobiol Aging. 2018 Apr;64:160.e9-160.e12. doi: 10.1016/j.neurobiolaging.2017.12.017. Epub 2017 Dec 27.
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 the TIA1 gene has been performed in Chinese patients with ALS and FTD. In this study, we screened the low-complexity domain of TIA1 in 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 the TIA1 gene in patients with ALS and FTD in Chinese population. Our findings broaden the known mutational spectrum in patients with ALS and further confirm TIA1 as a novel causative gene of ALS.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是大脑和脊髓中的运动神经元逐渐丧失。额颞叶痴呆（FTD）是一组以行为、执行功能和语言障碍逐渐恶化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，在白种人 ALS 和 ALS-FTD 患者中发现了 RNA 结合蛋白 T 细胞受限细胞内抗原-1（TIA1）基因低复杂度结构域的罕见突变。然而，尚未对中国 ALS 和 FTD 患者的 TIA1 基因进行全面的突变分析。在这项研究中，我们在中国大陆的 241 名 ALS 和 51 名 FTD 患者中筛选了 TIA1 的低复杂度结构域。结果，在 2 名散发性 ALS 患者中发现了 2 种新的错义突变（p.P352L 和 p.I300T），而在 FTD 病例中未发现突变。据我们所知，这是首次在中国人群中对 ALS 和 FTD 患者的 TIA1 基因进行突变分析。我们的发现扩大了已知的 ALS 患者突变谱，并进一步证实 TIA1 是 ALS 的一个新的致病基因。
