A hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic ALS in Taiwan
A hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic ALS in Taiwan
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DOI：
10.1016/j.neurobiolaging.2012.05.002
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Lee, Yi-Chung
中科院分区：
文献类型：
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作者：
Tsai, Ching-Paio;Soong, Bing-Wen;Lee, Yi-Chung
C9ORF72基因中的GGGGCC六核苷酸重复扩增最近被确定为高加索人群家族性肌萎缩侧索硬化症（ALS）和额颞叶痴呆的重要原因。C9ORF72重复扩增在中国ALS人群中的作用很少受到关注。因此，我们对22名无血缘关系的家族性ALS （FALS）患者和102名汉族散发性ALS患者进行突变分析。4例FALS患者（18.2%;4/22）和2例散发性ALS患者（2.0%;2/102）发现C9ORF72突变。在300名健康对照者和118名没有C9ORF72突变的ALS患者中，C9ORF72重复数从3到15不等。1例fals -额颞叶痴呆患者左额叶皮质穿刺活检显示大量胞质TAR dna结合蛋白43 （TDP-43）内含物和轻微神经炎，符合B型额颞叶变性伴TDP-43 （FTLD-TDP）病理。本研究清楚地证明了C9ORF72六核苷酸重复扩增在台湾华人ALS队列中的存在和重要性，并支持了C9ORF72重复扩增在ALS中的全球存在。(C) 2012爱思唯尔公司版权所有。
A GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene was recently identified as an important cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Caucasian populations. The role of the C9ORF72 repeat expansion in ALS in Chinese populations has received little attention. We therefore performed mutation analyses in a Taiwanese cohort of 22 unrelated familial ALS (FALS) patients and 102 sporadic ALS patients of Han Chinese descent. The C9ORF72 mutation was found in 4 FALS (18.2%; 4/22) and 2 sporadic ALS patients (2.0%; 2/102). The C9ORF72 repeat numbers in the 300 healthy controls and the 118 ALS patients without the C9ORF72 mutation ranged from 3 to 15. Needle biopsy in the left frontal cortex of 1 patient with FALS-frontotemporal dementia revealed numerous cytoplasmic TAR DNA-binding protein 43 (TDP-43) inclusions and minimal neuritis, consistent with type B frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) pathology. This study clearly demonstrates the existence and importance of the C9ORF72 hexanucleotide repeat expansion in a Taiwanese ALS cohort of Chinese origin, and supports the global presence of the C9ORF72 repeat expansion in ALS. (C) 2012 Elsevier Inc. All rights reserved.