Andersen P M, Nilsson P, Ala-Hurula V, Keränen M L, Tarvainen I, Haltia T, Nilsson L, Binzer M, Forsgren L, Marklund S L
Department of Neurology, Umeå University Hospital, Sweden.
Nat Genet. 1995 May;10(1):61-6. doi: 10.1038/ng0595-61.
Recent reports have shown heterozygosity for some twenty different mutations in the CuZn-superoxide dismutase (CuZn-SOD) gene in familial amyotrophic lateral sclerosis (FALS), and analysed samples from patients have shown decreased enzymic activity. Here we report homozygosity for an exon 4 mutation, Asp90Ala in fourteen patients among four unrelated ALS families and four apparently sporadic ALS patients from Sweden and Finland. The erythrocyte CuZn-SOD activity is essentially normal. Our findings suggest that this CuZn-SOD mutation causes ALS by a gain of function rather than by loss, and that the Asp90Ala mutation is less detrimental than previously reported mutations.
最近的报告显示，在家族性肌萎缩侧索硬化症（FALS）中，铜锌超氧化物歧化酶（CuZn-SOD）基因存在约20种不同的突变杂合性，并且对患者样本的分析表明酶活性降低。在此，我们报告了来自瑞典和芬兰的四个不相关的肌萎缩侧索硬化症（ALS）家族中的14名患者以及四名明显散发的ALS患者中，第4外显子存在Asp90Ala突变的纯合性。红细胞铜锌超氧化物歧化酶活性基本正常。我们的研究结果表明，这种铜锌超氧化物歧化酶突变通过功能获得而非功能丧失导致肌萎缩侧索硬化症，并且Asp90Ala突变的有害性低于先前报道的突变。
