Analyses MAPT, GRN, and C9orf72 mutations in Chinese patients with frontotemporal dementia
Analyses MAPT, GRN, and C9orf72 mutations in Chinese patients with frontotemporal dementia
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分析中国额颞叶痴呆患者的 MAPT、GRN 和 C9orf72 突变
DOI：
10.1016/j.neurobiolaging.2016.05.013
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发表时间：
2016-10-01
影响因子：
4.2
通讯作者：
Shen, Lu
中科院分区：
文献类型：
--
作者：
Tang, Min;Gu, Xiaohua;Shen, Lu
额颞叶痴呆（FTD）是一种临床异质性神经退行性疾病，包括行为行为变异型FTD（bvFTD）、语义性痴呆、进行性非流利性失语（PNFA）、FTD-帕金森综合征和FTD-运动神经元疾病。迄今为止，在FTD患者中至少发现了8种致病基因。其中，微管相关蛋白tau（MAPT）、GRN和9号染色体开放阅读框72（C9 orf 72）基因的变异被认为是FTD的主要原因。迄今为止，尚未在中国人群中对这3个基因的突变进行全面分析。在这项研究中，我们筛选了来自中国大陆的52名患者的MAPT和GRN的所有外显子，以及C9 orf 72中的GGGGCC重复序列，其中包括38名bvFTD，7名PNFA，2名语义性痴呆和5名FTD-帕金森综合征。结果，在1例散发性和家族性PNFA患者中分别发现了2个新的MAPT突变（p.D177V和p.P513A），在1个FTD-帕金森综合征家系中发现了1个已知的MAPT突变（p.N279K）。此外，在1例散发性bvFTD患者中发现了GRN中报告的一种无义突变（p. Q300 Term）。最后，在任何情况下都没有检测到C9 orf 72中的致病性GGGGCC重复。据我们所知，这是第一份在中国人群中筛查FTD患者常见致病突变的队列报告。我们的研究结果表明，MAPT和GRN的变异是中国大陆FTD的常见原因。(C)2016 Elsevier Inc. All rights reserved.
Frontotemporal dementia (FTD) is a clinically heterogeneous neurodegenerative disorder, including behavior behavioral variant FTD (bvFTD), semantic dementia, progressive nonfluent aphasia (PNFA), FTD-parkinsonism, and FTD-motor neuron disease. To date, there are at least 8 causative genes identified in patients with FTD. Among them, variants in the microtubule-associated protein tau (MAPT), GRN, and chromosome 9 open-reading frame 72 (C9orf72) genes are considered the major cause of FTD. To date, no comprehensive analyses of mutations in these 3 genes have been conducted in the Chinese population. In this study, we screened all exons of MAPT, and GRN, as well as GGGGCC repeats in C9orf72 in a cohort of 52 patients from mainland China, including 38 bvFTD, 7 PNFA, 2 semantic dementia, and 5 FTD-parkinsonism. As a result, 2 novel mutations in MAPT (p. D177V and p. P513A) were identified in a sporadic and familial patient with PNFA respectively, and one known mutation in MAPT (p. N279K) was detected in an FTD-parkinsonism family. In addition, one reported nonsense mutation (p. Q300Term) in GRN was found in a sporadic patient with bvFTD. Finally, no pathogenic GGGGCC repeats in C9orf72 were detected in any case. To our knowledge, this is the first cohort report screening for common causative mutations in patients with FTD in the Chinese population. Our findings indicate that variants of MAPT and GRN are a common cause of FTD in mainland China. (C) 2016 Elsevier Inc. All rights reserved.