Department of Neurology, Hanyang University College of Medicine, Seoul, South Korea.
J Neurol Sci. 2011 Jul 15;306(1-2):157-9. doi: 10.1016/j.jns.2011.03.041. Epub 2011 Apr 14.
We identified a novel missense mutation in the Cu/Zn superoxide dismutase (SOD1) gene in a 47-year-old woman with familial amyotrophic lateral sclerosis (ALS). The heterozygous mutation, in exon 1 of the SOD1 gene, is a GC to TT transversion in nucleotide positions 13 and 14 leading to an alanine 4 to phenylalanine (A4F) amino acid substitution. It was found in six family members. The effect of the A4F mutation was of similar severity to that of the A4V mutation. We discuss structural instability as a possible pathogenic mechanism in the case of this SOD1 mutation. The proband displayed upper motor neuron signs not observed in individuals with other codon 4 mutations. This could be because longer survival allows UMN dysfunction to become evident. We also provide a literature review.
我们在一位 47 岁的家族性肌萎缩侧索硬化症（ALS）女性中发现了铜/锌超氧化物歧化酶（SOD1）基因中的一个新的错义突变。该杂合突变位于 SOD1 基因的外显子 1 中，是核苷酸位置 13 和 14 的 GC 到 TT 颠换，导致丙氨酸 4 到苯丙氨酸（A4F）的氨基酸取代。该突变在六个家族成员中被发现。A4F 突变的影响与 A4V 突变的相似严重程度。我们讨论了结构不稳定性作为这种 SOD1 突变的可能致病机制。该先证者表现出上运动神经元体征，而在其他密码子 4 突变的个体中没有观察到这些体征。这可能是因为较长的生存时间使 UMN 功能障碍变得明显。我们还提供了文献综述。
