期刊
NEUROBIOLOGY OF AGING
卷 38, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.11.016
关键词
C9orf72; Amyotrophic lateral sclerosis; Haplotype analysis; Southern blotting; Cognitive impairment; Meta-analysis; Chinese population
资金
- Howard Hughes Medical Institute at Massachusetts Institute of Technology
- National Science Fund of China [81371394]
- Science and Technology Bureau Fund of Sichuan Province [2014FZ0072]
An intronic GGGGCC hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9orf72) gene was considered as the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Caucasian populations. Using repeat-primed polymerase chain reaction analysis and Southern blotting methods, we assessed the frequency and size of hexanucleotide repeat expansion in a cohort of 918 sporadic ALS (SALS) patients and 632 control individuals of Han Chinese origin. We identified 8 (0.87%) of the SALS patients and none of control individuals as carriers of C9orf72 expansions with 700-3500 repeats. A comprehensive neuropsychological battery was conducted on 4 expansion-positive ALS patients, where 3 patients were found to have cognitive impairment. All expansion-positive patients were genotyped for the previously reported 20 single-nucleotide polymorphism (SNP) risk haplotypes on chromosome 9p21. Among them, 13 SNP risk haplotypes were shared in all expansion carriers, suggesting a common founder from European ancestry. Further meta-analysis demonstrated that the intermediate expansion size with 24-30 repeats, rare in both patients and controls, were significantly associated with the risk for ALS. To our knowledge, this is the first study to identify a proportion of Chinese SALS patients carrying this pathologic expansion of up to similar to 3500 repeats and to completely elaborate the 20-SNP risk haplotypes in Chinese expansion-positive patients, providing indispensable evidence for the origin, geographical range, and population prevalence of the C9orf72-associated ALS. (C) 2016 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据