Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
Neurobiol Aging. 2012 May;33(5):1016.e1-7. doi: 10.1016/j.neurobiolaging.2011.05.019. Epub 2011 Jul 28.
Optineurin (OPTN) mutations have been reported in a cohort of Japanese patients with familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis. In Caucasian patients, OPTN mutations have been identified in FALS patients, but were not detected in a cohort of 95 SALS patients. Moreover, single nucleotide polymorphisms (SNPs) in OPTN that could raise amyotrophic lateral sclerosis (ALS) susceptibility have not been investigated. Therefore, we screened a large Dutch cohort of 1191 patients with SALS, 94 patients with FALS, and 1415 control subjects for mutations and SNPs in OPTN. We identified 1 novel nonsense mutation (Q165X) and 1 unreported missense mutation (Q454E) in individual SALS patients. These patients demonstrated rapid disease progression with an average survival of 24.5 months. No heterozygous or homozygous OPTN mutations were identified in our cohort of FALS patients. SNP analysis did not reveal significant differences between ALS patients and control subjects. Therefore, variations in OPTN appear to be a rare cause of rapidly progressive SALS in the Netherlands.
已在一组日本家族性（FALS）和散发性（SALS）肌萎缩侧索硬化症患者中报道了 OPTN 突变。在白种人患者中，已在 FALS 患者中鉴定出 OPTN 突变，但在 95 名 SALS 患者的队列中未检测到。此外，尚未研究可能增加肌萎缩侧索硬化症（ALS）易感性的 OPTN 单核苷酸多态性（SNP）。因此，我们筛选了一个由 1191 名 SALS 患者、94 名 FALS 患者和 1415 名对照组成的大型荷兰队列，以寻找 OPTN 中的突变和 SNP。我们在个别 SALS 患者中发现了 1 种新的无义突变（Q165X）和 1 种未报告的错义突变（Q454E）。这些患者表现出快速的疾病进展，平均生存时间为 24.5 个月。在我们的 FALS 患者队列中未发现杂合或纯合 OPTN 突变。SNP 分析未显示 ALS 患者与对照组之间存在显着差异。因此，OPTN 的变异似乎是荷兰快速进展性 SALS 的罕见原因。
