Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark.
Neurobiol Aging. 2012 Jan;33(1):208.e1-5. doi: 10.1016/j.neurobiolaging.2011.07.001. Epub 2011 Aug 26.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. About 10% of ALS cases are familial (FALS) and the genetic defect is known only in approximately 20%-30% of these cases. The most common genetic cause of ALS is SOD1 (superoxide dismutase 1) mutation. Very recently, mutations of the optineurin gene (OPTN), which is involved in open-angle glaucoma, were identified in 3 Japanese patients/families with ALS, and subsequently in a few FALS patients of European descent. We found a heterozygous nonsense mutation (c.493C>T, p.Gln165X, exon 6) in the OPTN gene in a Danish patient with ALS, and the mutation segregated from his affected father. The p.Gln165X mutation could not be detected in 1070 healthy Danish controls, in 1000 Danish individuals with metabolic phenotypes or in 64 sporadic ALS (SALS) cases. The p.Gln165X mutation described in this study is the first mutation reported in a Danish family and is likely involved in disease pathogenesis. Until now, only few OPTN mutations have been associated with ALS. As the underlying genetic defect is known only in approximately 20%-30% of FALS families, further screening of these cases is necessary for establishing the contribution of OPTN mutations in disease pathogenesis.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病。约 10%的 ALS 病例为家族性（FALS），而这些病例中只有约 20%-30%的遗传缺陷是已知的。ALS 的最常见遗传原因是 SOD1（超氧化物歧化酶 1）突变。最近，参与开角型青光眼的视神经病变基因（OPTN）的突变在 3 名日本 ALS 患者/家族中被发现，随后在一些欧洲血统的 FALS 患者中也被发现。我们在一名丹麦 ALS 患者的 OPTN 基因中发现了一个杂合的无义突变（c.493C>T，p.Gln165X，外显子 6），该突变与他患病的父亲分离。在 1070 名健康的丹麦对照、1000 名具有代谢表型的丹麦个体和 64 名散发性 ALS（SALS）病例中，均未检测到 p.Gln165X 突变。本研究中描述的 p.Gln165X 突变是在丹麦家族中报告的第一个突变，可能与疾病发病机制有关。到目前为止，只有少数 OPTN 突变与 ALS 相关。由于只有约 20%-30%的 FALS 家族的遗传缺陷是已知的，因此需要对这些病例进行进一步筛查，以确定 OPTN 突变在疾病发病机制中的作用。
