Copper/zinc superoxide dismutase 1 and sporadic amyotrophic lateral sclerosis: Analysis of 155 cases and identification of novel insertion mutation
Copper/zinc superoxide dismutase 1 and sporadic amyotrophic lateral sclerosis: Analysis of 155 cases and identification of novel insertion mutation
复制标题
铜/锌超氧化物歧化酶1与散发性肌萎缩侧索硬化症：155例病例分析及新插入突变的鉴定
作者：
M. Jackson;A. Al;Z. Enayat;B. Chioza;P. Leigh;K. Morrison
肌萎缩侧索硬化症 (ALS) 是一种进行性麻痹性疾病，由大脑和脊髓运动神经元退化引起，可导致症状出现 5 年内死亡。绝大多数 ALS 病例都是散发性的，其中家族型 (FALS) 占所有病例的比例不到 10%。铜/锌超氧化物歧化酶 1 (SOD-1) 基因突变此前已被确定为约 20% FALS 病例的根本原因。由于该疾病的家族性和散发性形式在临床上相似，我们试图确定 SOD-1 的此类突变是否是任何散发性 ALS 病例的基础。我们通过单链构象多态性筛查了155例散发病例，鉴定出4例SOD-1基因外显子4具有点突变的散发病例。其中两个突变与之前在 FALS 病例中报道的突变相同。一个突变是新的，由于 G（外显子 4 最后一个密码子的第一个碱基）被 AAAAC 替换，导致 Val118 发生移码。由于在外显子 5 中引入了三个残基的终止密码子，该突变导致 SOD-1 蛋白被截短。
Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder resulting from the degeneration of motor neurons in the brain and spinal cord and leading to death within 5 years of symptom onset. The great majority of ALS cases are sporadic, with the familial form (FALS) representing fewer than 10% of all cases. Mutations in the copper/zinc superoxide dismutase 1 (SOD‐1) gene have previously been identified as the underlying cause of approximately 20% of FALS cases. As the familial and sporadic forms of the disease are clinically similar, we have sought to determine whether such mutations in SOD‐1 underlie any sporadic ALS cases. We have screened 155 sporadic cases by single‐strand conformation polymorphism and have identified 4 sporadic cases that possess point mutations in exon 4 of the SOD‐1 gene. Two of these mutations are identical to those previously reported in FALS cases. One mutation is novel, resulting in a frameshift at Val118 due to the replacement of G (first base in the last codon of exon 4) by AAAAC. This mutation results in a truncated SOD‐1 protein due to the introduction of a stop codon three residues into exon 5.
影响因子：
9.8
作者：
A. Pramatarova;D. Figlewicz;A. Krizus;Fei-yu Han;I. Ceballos-Picot;A. Nicole;M. Dib;V. Meininger;Robert H. Brown;G. Rouleau
通讯作者：
A. Pramatarova;D. Figlewicz;A. Krizus;Fei-yu Han;I. Ceballos-Picot;A. Nicole;M. Dib;V. Meininger;Robert H. Brown;G. Rouleau
影响因子：
158.5
作者：
SIDDIQUE, T;FIGLEWICZ, DA;ROSES, AD
通讯作者：
ROSES, AD