Genetic Features of MAPT, GRN, C9orf72 and CHCHD10 Gene Mutations in Chinese Patients with Frontotemporal Dementia
Genetic Features of MAPT, GRN, C9orf72 and CHCHD10 Gene Mutations in Chinese Patients with Frontotemporal Dementia
复制标题
DOI：
10.2174/1567205014666170426105713
复制
发表时间：
2017-01-01
影响因子：
2.1
通讯作者：
Guo, Qi-Hao
中科院分区：
文献类型：
--
作者：
Che, Xiang-Qian;Zhao, Qian-Hua;Guo, Qi-Hao
背景：据报道，微管相关蛋白 tau (MAPT)、颗粒体蛋白前体 (GRN)、9 号染色体开放阅读框 72 (C9orf72) 和 CHCHD10 基因的突变可导致不同人群的额颞叶痴呆 (FTD)。然而，对中国 FTD 患者这四种基因突变的集体分析尚未见报道。 方法：本研究的目的是在中国上海大都市地区多个临床中心招募的 FTD 队列中调查中国 MAPT、GRN、C9orf72 或 CHCHD10 基因突变患者的遗传特征。通过直接测序分析 MAPT、GRN 和 CHCHD10 基因，通过重复引物 PCR 对 82 名散发性 FTD 患者的 C9orf72 六核苷酸重复扩增进行分析。在400名年龄匹配的对照中筛选出已鉴定的基因变异。结果：我们发现MAPT基因1个已知致病变异（rs63750959）和1个新突变（NG_007398.1：g.120962C> T;H299Y），GRN基因1个新变异（c.750C>A; D250E）和CHCHD10基因2个新突变 (c.63C>T，无AA变化；c.71G>A，P24L)。在该队列中未发现异常的 C9orf72 基因六核苷酸重复扩增。总的来说，基因检测可以发现 4.9% 的散发性 FTD 患者有遗传原因。此外，MAPT和CHCHD10可能是影响中国人FTD的更重要基因。
Background: Mutations in microtubule associated protein tau (MAPT), progranulin (GRN), chromosome 9 open-reading frame 72 (C9orf72) and CHCHD10 genes have been reported causing frontotemporal dementia (FTD) in different populations. However, collective analysis of mutations in these four genes in Chinese FTD patients has not been reported yet.Methods: The aim of this study was to investigate the genetic features of Chinese patients with MAPT, GRN, C9orf72 or CHCHD10 gene mutations in an FTD cohort recruited from multi clinical centers in Shanghai metropolitan areas, China. MAPT, GRN and CHCHD10 genes were analysed by direct sequencing, and C9orf72 hexanucleotide repeat expansion was analysed by repeat-primed PCR in 82 patients with sporadic FTD. The identified gene variants were screened in 400 age matched controls.Results: We found one known pathogenic variant (rs63750959) and one novel mutation (NG_007398.1: g.120962C> T;H299Y) of MAPT gene, one novel variant (c.750C>A; D250E) of GRN gene and two novel mutations in CHCHD10 gene (c.63C>T, no AA change; c.71G>A, P24L). No abnormal C9orf72 gene hexanucleotide repeat expansion was identified in this cohort. Collectively, genetic testing could discover 4.9% sporadic FTD patients with genetic causes. In addition, MAPT and CHCHD10 might be more important genes affecting Chinese with FTD.