Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis.
Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis.
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发表时间：
1995-03
影响因子：
9.8
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
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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
肌萎缩侧索硬化症（ALS）是一种影响运动神经元的致命性神经退行性疾病。虽然大多数ALS病例是散发性的，但大约10%是作为常染色体显性遗传的。Cu/Zn超氧化物歧化酶基因（SOD 1）的突变是部分家族性ALS（FALS）的原因。通过SSCP筛选我们的FALS激酶，我们在15个家庭中发现了突变，其中9个以前从未报道过。其中两个新的突变改变了从未与FALS有关的氨基酸。其中一个影响二聚体接触中涉及的高度保守的氨基酸，另一个影响酶的活性位点环。这两种突变均显著降低淋巴母细胞SOD 1酶活性。我们的研究结果表明，SOD 1基因突变与>或= 13%的FALS病例有关.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting motor neurons. Although most cases of ALS are sporadic, approximately 10% are inherited as an autosomal dominant trait. Mutations in the Cu/Zn superoxide dismutase gene (SOD 1) are responsible for a fraction of familial ALS (FALS). Screening our FALS kindreds by SSCP, we have identified mutations in 15 families, of which 9 have not been previously reported. Two of the new mutations alter amino acids that have never been implicated in FALS. One of them affects a highly conserved amino acid involved in dimer contact, and the other one affects the active-site loop of the enzyme. These two mutations reduce significantly SOD 1 enzyme activity in lymphoblasts. Our results suggest that SOD 1 mutations are responsible for > or = 13% of FALS cases.