Identification of C9orf72 repeat expansions in patients with amyotrophic lateral sclerosis and frontotemporal dementia in mainland China
Identification of C9orf72 repeat expansions in patients with amyotrophic lateral sclerosis and frontotemporal dementia in mainland China
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中国大陆肌萎缩侧索硬化症和额颞叶痴呆患者 C9orf72 重复扩增的鉴定
DOI：
10.1016/j.neurobiolaging.2013.10.001
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发表时间：
2014-04-01
影响因子：
4.2
通讯作者：
Shen, Lu
中科院分区：
文献类型：
--
作者：
Jiao, Bin;Tang, Beisha;Shen, Lu
C9 orf 72基因中的GGGGCC重复扩增最近被确定为白色人群中肌萎缩侧索硬化（ALS）和额颞叶痴呆（FTD）的主要原因。为了估计来自中国大陆的ALS和FTD患者中六核苷酸重复的频率，我们使用重复引物聚合酶链反应方法在128名患者和150名对照受试者的队列中筛查C9 orf 72。我们在一个ALS-FTD家族和一个散发性FTD患者中观察到致病性重复扩增。在ALS-FTD家族中，先证者和2名无症状同胞表现出C9 orf 72重复扩增，先证者的临床特征为无认知障碍的纯运动综合征。散发性FTD患者主要表现为行为和精神状态恶化。基因型分析显示，先证者与先前报告的20个单核苷酸多态性风险单倍型相同，而散发性FTD患者携带除rs 2814707-A外的所有单核苷酸多态性。据我们所知，该研究首次在中国大陆报告了2例C9 orf 72突变患者，他们具有在白色人群中发现的相似风险单倍型，表明与C9 orf 72突变相关的ALS和FTD可能来自同一创始人。(C)2014 Elsevier Inc. All rights reserved.
The GGGGCC repeat expansion in the C9orf72 gene was recently identified as a major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in white populations. To estimate the frequency of hexanucleotide repeats in patients with ALS and FTD from mainland China, we screened for C9orf72 in a cohort of 128 patients and 150 control subjects using the repeat-primed polymerase chain reaction method. We observed pathogenic repeat expansions in a family with ALS-FTD and in a patient with sporadic FTD. In the family with ALS-FTD, the proband and the 2 asymptomatic siblings exhibited C9orf72 repeat expansions, and the clinical feature of the proband was characterized by pure motor syndrome with no cognitive impairment. The patient with sporadic FTD presented primarily with deteriorating behavior and mental status. Genotype analysis revealed that the proband shared the previously reported 20-single nucleotide polymorphism risk haplotype, whereas the patient with sporadic FTD carried all single nucleotide polymorphisms except rs2814707-A. To our knowledge, this study is the first to report 2 C9orf72 mutation patients in mainland China, and they shared the similar risk haplotype identified in white populations, suggesting that ALS and FTD associated with C9orf72 mutation was probably derived from a single founder. (C) 2014 Elsevier Inc. All rights reserved.