Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney, 2139, Australia.
Neurobiol Aging. 2012 Jan;33(1):210.e9-10. doi: 10.1016/j.neurobiolaging.2011.09.023. Epub 2011 Oct 19.
Mutations in the optineurin gene (OPTN) have been reported in rare familial and sporadic amyotrophic lateral sclerosis (ALS) cases. It is yet to be established whether mutations segregate with dominantly inherited familial ALS. We therefore performed mutation analysis in a cohort of 96 autosomal dominant ALS families. A novel heterozygous nonsynonymous variant (c.218C > T, S73L) was identified in one patient; however, analysis in the extended pedigree demonstrated that this variant was inherited from an unaffected parent. The variant was absent in 480 control individuals. The affected serine residue is highly conserved and its substitution is predicted to alter phosphorylation. Despite this, our evidence indicates that this variant is unlikely to play a pathogenic role in the disease. Cell and animal models will be required to functionally support the pathogenic role of OPTN mutations.
已经在罕见的家族性和散发性肌萎缩侧索硬化症（ALS）病例中报道了视神经萎缩症基因（OPTN）的突变。是否突变与显性遗传家族性 ALS 分离还有待确定。因此，我们在 96 个常染色体显性 ALS 家族的队列中进行了突变分析。在一名患者中发现了一种新的杂合非同义变异（c.218C > T，S73L）；然而，对扩展家系的分析表明，该变异是从未受影响的父母遗传的。该变体在 480 名对照个体中不存在。受影响的丝氨酸残基高度保守，其取代被预测会改变磷酸化。尽管如此，我们的证据表明该变体不太可能在疾病中发挥致病作用。需要细胞和动物模型来从功能上支持 OPTN 突变的致病作用。
