Cudkowicz M E, McKenna-Yasek D, Sapp P E, Chin W, Geller B, Hayden D L, Schoenfeld D A, Hosler B A, Horvitz H R, Brown R H
Day Neuromuscular Research Laboratory, Massachusetts General Hospital East, Charlestown, USA.
Ann Neurol. 1997 Feb;41(2):210-21. doi: 10.1002/ana.410410212.
We registered 366 families in a study of dominantly inherited amyotrophic lateral sclerosis. Two hundred ninety families were screened for mutations in the gene encoding copper-zinc cytosolic superoxide dismutase (SOD1). Mutations were detected in 68 families. The most common SOD1 mutation is an alanine for valine substitution in codon 4 (50%). We present clinical and genetic data concerning 112 families with 395 affected individuals. The clinical characteristics of patients with familial amyotrophic lateral sclerosis arising from SOD1 mutations are similar to those lacking SOD1 defects. Mean age at onset was earlier (Wilcoxon test, p = 0.004) in the SOD1 group (46.9 years [standard deviation, 12.5] vs 50.5 years [11.5] in the non-SOD1 group). Bulbar onset was associated with a later onset age. The presence of either of two mutations, G37R and L38V, predicted an earlier age at onset. Kaplan-Meier plots demonstrated shorter survival in the SOD1 group compared with the non-SOD1 group at early survival times (Wilcoxon test, p = 0.0007). The presence of one mutation, A4V, correlated with shorter survival. G37R, G41D, and G93C mutations predicted longer survival. This information suggests it will be productive to investigate other genetic determinants in amyotrophic lateral sclerosis and to use epidemiological characteristics of the disease to help discern molecular mechanisms of motor neuron cell death.
我们在一项关于显性遗传性肌萎缩侧索硬化症的研究中登记了366个家庭。对290个家庭进行了编码铜锌胞质超氧化物歧化酶（SOD1）基因的突变筛查。在68个家庭中检测到了突变。最常见的SOD1突变是密码子4处丙氨酸替代缬氨酸（50%）。我们呈现了112个家庭中395名患者的临床和遗传数据。由SOD1突变引起的家族性肌萎缩侧索硬化症患者的临床特征与无SOD1缺陷的患者相似。SOD1组的平均发病年龄更早（Wilcoxon检验，p = 0.004）（46.9岁[标准差，12.5]，而非SOD1组为50.5岁[11.5]）。延髓起病与发病年龄较晚相关。G37R和L38V这两种突变中的任何一种的存在都预示着发病年龄较早。Kaplan-Meier曲线显示，在早期生存阶段，SOD1组的生存率低于非SOD1组（Wilcoxon检验，p = 0.0007）。A4V这一突变的存在与较短的生存期相关。G37R、G41D和G93C突变预示着较长的生存期。这些信息表明，研究肌萎缩侧索硬化症的其他遗传决定因素以及利用该疾病的流行病学特征来帮助识别运动神经元细胞死亡的分子机制将是有成效的。
