Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Neurobiol Aging. 2012 Dec;33(12):2950.e5-7. doi: 10.1016/j.neurobiolaging.2012.07.005. Epub 2012 Jul 26.
Expansions of the noncoding GGGGCC hexanucleotide repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In this study we aimed to determine whether the length of the normal-unexpanded-allele of the GGGGCC repeat in C9ORF72 plays a role in the presentation of disease or affects age at onset in C9ORF72 mutation carriers. We also studied whether the GGGGCC repeat length confers risk or affects age at onset in FTD and ALS patients without C9ORF72 repeat expansions. C9ORF72 genotyping was performed in 580 FTD, 995 ALS, and 160 FTD-ALS patients, and 1444 controls, leading to the identification of 211 patients with pathogenic C9ORF72 repeat expansions. No meaningful association between the repeat length of the normal alleles of the GGGGCC repeat in C9ORF72 and disease phenotype or age at onset was observed in C9ORF72 mutation carriers or nonmutation carriers.
GGGCCC 六核苷酸重复序列在 9 号染色体开放阅读框 72（C9ORF72）基因中的扩展会导致额颞叶痴呆（FTD）和肌萎缩侧索硬化症（ALS）。在这项研究中，我们旨在确定 C9ORF72 中 GGGGCC 重复的正常未扩展等位基因的长度是否在疾病表现中起作用或影响 C9ORF72 突变携带者的发病年龄。我们还研究了 GGGGCC 重复长度是否在没有 C9ORF72 重复扩展的 FTD 和 ALS 患者中赋予风险或影响发病年龄。对 580 名 FTD、995 名 ALS 和 160 名 FTD-ALS 患者以及 1444 名对照者进行了 C9ORF72 基因分型，鉴定出 211 名具有致病性 C9ORF72 重复扩展的患者。在 C9ORF72 突变携带者或非突变携带者中，未观察到 C9ORF72 中 GGGGCC 重复的正常等位基因重复长度与疾病表型或发病年龄之间存在有意义的关联。
