Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype.
Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype.
复制标题
C9ORF72 GGGGCC重复序列的正常等位基因长度不影响疾病表型。
DOI：
10.1016/j.neurobiolaging.2012.07.005
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发表时间：
2012-12
影响因子：
4.2
通讯作者：
Rademakers R
中科院分区：
文献类型：
--
作者：
Rutherford NJ;Heckman MG;Dejesus-Hernandez M;Baker MC;Soto-Ortolaza AI;Rayaprolu S;Stewart H;Finger E;Volkening K;Seeley WW;Hatanpaa KJ;Lomen-Hoerth C;Kertesz A;Bigio EH;Lippa C;Knopman DS;Kretzschmar HA;Neumann M;Caselli RJ;White CL 3rd;Mackenzie IR;Petersen RC;Strong MJ;Miller BL;Boeve BF;Uitti RJ;Boylan KB;Wszolek ZK;Graff-Radford NR;Dickson DW;Ross OA;Rademakers R
9 号染色体开放阅读框 72 (C9ORF72) 基因中非编码 GGGGCC 六核苷酸重复的扩展最近被确定为 9p 染色体上额颞叶痴呆 (FTD) 和肌萎缩侧索硬化症 (ALS) 的长期追寻的病因。在本研究中，我们旨在确定 C9ORF72 中 GGGGCC 重复序列的正常未扩增等位基因的长度是否在 C9ORF72 突变携带者的疾病表现中发挥作用或影响发病年龄。我们还研究了 GGGGCC 重复长度是否会带来风险或影响没有 C9ORF72 重复扩增的 FTD 和 ALS 患者的发病年龄。对 580 名 FTD、995 名 ALS 和 160 名 FTD-ALS 患者以及 1444 名对照进行了 C9ORF72 基因分型，从而鉴定出 211 名具有致病性 C9ORF72 重复扩增的患者，并对所有患者和对照中正常等位基因的长度进行了准确量化。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的重复长度与疾病表型或发病年龄之间存在有意义的关联。
Expansions of the non-coding GGGGCC hexanucleotide repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene were recently identified as the long sought-after cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) on chromosome 9p. 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 and an accurate quantification of the length of the normal alleles in all patients and controls. 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 non-mutation carriers.