Valdmanis Paul N, Daoud Hussein, Dion Patrick A, Rouleau Guy A
Center of Excellence in Neuromics of the CHUMResearch Center and the Department of Medicine,University of Montreal, 1560 Sherbrooke Street East, Room Y-3633, Montreal QCH2L4M1, Canada.
Curr Neurol Neurosci Rep. 2009 May;9(3):198-205. doi: 10.1007/s11910-009-0030-9.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with a low survival rate beyond 5 years from symptom onset. Although the genes that cause most cases of ALS are still unknown, several important genetic discoveries have been made recently that will bring substantial insight into some of the mechanisms involved in ALS. Mutations in two genes with related functions were recently reported in patients with familial ALS: the FUS/TLS gene at the ALS6 locus on chromosome 16 and the TARDBP gene at the ALS10 locus on chromosome 1. In addition, the first wave of genomewide association studies in ALS has been published. While these studies clearly show that there is no definitive and common highly penetrant allele that causes ALS, some interesting candidate genes emerged from these studies. The findings help to better delineate the types of genes and genetic variants that are involved in ALS and provide substantial material for future research.
肌萎缩侧索硬化症（ALS）是一种毁灭性的神经退行性疾病，从症状出现起5年后生存率较低。尽管导致大多数ALS病例的基因仍不明确，但最近有几项重要的遗传学发现，这将为ALS所涉及的一些机制带来实质性的见解。最近在家族性ALS患者中报道了两个具有相关功能的基因突变：位于16号染色体ALS6位点的FUS/TLS基因和位于1号染色体ALS10位点的TARDBP基因。此外，ALS的首批全基因组关联研究已经发表。虽然这些研究清楚地表明，不存在导致ALS的明确且常见的高 penetrance 等位基因，但这些研究中出现了一些有趣的候选基因。这些发现有助于更好地描绘参与ALS的基因类型和遗传变异，并为未来的研究提供大量素材。
