Two distinct clinical features and cognitive impairment in amyotrophic lateral sclerosis patients with TARDBP gene mutations in the Chinese population
Two distinct clinical features and cognitive impairment in amyotrophic lateral sclerosis patients with TARDBP gene mutations in the Chinese population
复制标题
中国人群 TARDBP 基因突变肌萎缩侧索硬化症患者的两种不同临床特征和认知障碍
DOI：
10.1016/j.neurobiolaging.2015.10.032
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发表时间：
2016-02-01
影响因子：
4.2
通讯作者：
Deng, Min
中科院分区：
文献类型：
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作者：
Ju, XiaoDong;Liu, WenChao;Deng, Min
TARDBP基因突变已被确定为肌萎缩性侧索硬化症（ALS）的主要致病因素。然而，很少有报道分析基因型与表型的关系，特别是在中国ALS患者中。我们的研究调查了中国ALS患者TARDBP突变的存在和频率。此外，我们还研究了一个带有p.M337 V突变的ALS大家族和一个带有p.S393 L突变的散发性ALS （SALS）患者的临床特征与TARDBP基因突变的相关性。携带p.m 337v突变的家系表现出不同的临床特征，寿命长，特别是认知障碍。一名携带p.S393 L突变的患者经历了ALS伴认知障碍；患者也有额颞叶痴呆（FTD）家族史。这是中国人群TARDBP基因详细的遗传和临床特征的第一份报告。这项研究也首次证明了p.M337 V和p.S393 L突变与ALS患者的认知障碍有关。中国sod1阴性家族性ALS （FALS）中TARDBP的突变频率为5.6%，远高于以往在高加索人群中进行的研究，而中国人群中SALS患者的TARDBP突变频率较低。我们的研究结果强调了ALS中TARDBP突变的遗传和临床特征的重要性，这使我们能够了解不同人群的基因型-表型关系和相对频率。(C) 2016 Elsevier Inc.版权所有。
Mutations in the TARDBP gene have been identified as a major causative factor in amyotrophic lateral sclerosis (ALS). However, few reports have analyzed the relationship of genotype-phenotype, especially in Chinese ALS patients. Our study investigated the presence and frequency of TARDBP mutations in Chinese patients with ALS. Additionally, we investigated correlations among clinical features and TARDBP gene mutations in a large ALS family with the p.M337 V mutation and one sporadic ALS (SALS) patient with the p.S393 L mutation. The pedigree with the p.M337 V mutation showed variable clinical features with a long lifespan, particularly cognitive impairment. One patient carrying the p.S393 L mutation experienced ALS with cognitive impairment; the patient also had a family history of frontotemporal dementia (FTD). This is the first report of detailed genetic and clinical characterizations of the TARDBP gene in a Chinese population. This research is also the first to demonstrate that the p.M337 V and the p.S393 L mutations are related to cognitive impairment in ALS patients. The mutation frequency of TARDBP was 5.6% in Chinese, SOD1-negative familial ALS (FALS), which was much higher than that reported in previous studies conducted with Caucasian populations, whereas the TARDBP mutation frequency was lower in the Chinese population with regard to SALS patients. Our results emphasize the importance of the genetic and clinical characterization of TARDBP mutations in ALS, which allows us to understand the genotypeephenotype relationship and relative frequencies in different populations. (C) 2016 Elsevier Inc. All rights reserved.