筛查与 ALS 和额颞叶痴呆相关的基因座上新的六核苷酸重复扩展。
Screening for novel hexanucleotide repeat expansions at ALS- and FTD-associated loci.
机构信息
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
出版信息
Neurol Genet. 2016 May 11;2(3):e71. doi: 10.1212/NXG.0000000000000071. eCollection 2016 Jun.
OBJECTIVE
To determine whether GGGGCC (G4C2) repeat expansions at loci other than C9orf72 serve as common causes of amyotrophic lateral sclerosis (ALS).
METHODS
We assessed G4C2 repeat number in 28 genes near known ALS and frontotemporal dementia (FTD) loci by repeat-primed PCR coupled with fluorescent fragment analysis in 199 patients with ALS (17 familial, 182 sporadic) and 136 healthy controls. We also obtained blood from patients with ALS4 for evaluation of repeats surrounding the SETX gene locus. C9orf72 expansions were evaluated in parallel.
RESULTS
Expansions of G4C2 repeats in C9orf72 explained 8.8% of sporadic and 47% of familial ALS cases analyzed. Repeat variance was observed at one other locus, RGS14, but no large expansions were observed, and repeat sizes were not different between cases and controls. No G4C2 repeat expansions were identified at other ALS or FTD risk loci or in ALS4 cases.
CONCLUSIONS
G4C2 expansions near known ALS and FTD loci other than C9orf72 are not a common cause of ALS.
目的
确定 C9orf72 以外的其他 GGGGCC(G4C2)重复扩展是否为肌萎缩侧索硬化症（ALS）的常见病因。
方法
我们通过重复引物 PCR 结合荧光片段分析，评估了 199 名 ALS 患者（17 名家族性，182 名散发性）和 136 名健康对照者中 28 个已知 ALS 和额颞叶痴呆（FTD）基因座附近的 G4C2 重复数。我们还从 ALS4 患者中获得血液，以评估 SETX 基因座周围的重复序列。同时评估 C9orf72 扩展。
结果
分析的散发性和家族性 ALS 病例中，C9orf72 中的 G4C2 重复扩展分别解释了 8.8%和 47%。在另一个 RGS14 基因座观察到重复变异，但未观察到大片段扩展，并且病例和对照组之间的重复大小没有差异。在其他 ALS 或 FTD 风险基因座或 ALS4 病例中未发现 G4C2 重复扩展。
结论
C9orf72 以外的其他已知 ALS 和 FTD 基因座附近的 G4C2 重复扩展不是 ALS 的常见病因。
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