Familial Amyotrophic Lateral Sclerosis with a Novel G85S Mutation of Superoxide Dismutase 1 Gene: Clinical Features of Lower Motor Neuron Disease
Familial Amyotrophic Lateral Sclerosis with a Novel G85S Mutation of Superoxide Dismutase 1 Gene: Clinical Features of Lower Motor Neuron Disease
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DOI：
10.2169/internalmedicine.49.2720
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发表时间：
2010-01-01
影响因子：
1.2
通讯作者：
Iwasaki, Yasuo
中科院分区：
文献类型：
--
作者：
Takazawa, Takanori;Ikeda, Ken;Iwasaki, Yasuo
肌萎缩侧索硬化症（ALS）是一种以上下运动神经元损伤为特征的毁灭性疾病。Cu/Zn超氧化物歧化酶（SOD 1）基因突变占家族性ALS（familial ALS，FALS）的20%。我们报告一个独特的临床基因型的一个日本家庭与一个新的SOD 1突变。一名37岁的女性（先证者）注意到左下肢肌肉无力。她的母亲在38岁时四肢出现进行性下运动神经元体征。随后，她被诊断为ALS，并在临床发作后15个月死于呼吸衰竭。先证者的神经系统检查显示左膝和左踝肌牵张反射消失，无巴宾斯基征。左下肢存在轻中度肌无力。左大腿出现肌肉萎缩。初始肺功能显示用力肺活量为91.1%。肌电图显示左下肢持续失神经肌肉电位。SOD 1分析表明外显子4的第85位密码子（G85 S）处甘氨酸被丝氨酸取代。6个月后，明显的肌肉无力和萎缩扩展到四肢。所有肌肉牵张反射均不存在。三个月后，需要呼吸机支持和气管造口术。患者在临床发作后18个月死亡。该FALS家族的临床特征表明，SOD 1的G85 S突变可能导致纯下运动神经元体征的快速进展形式。
Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by upper and lower motor neuron damage. Mutations of Cu/Zn superoxide dismutase gene (SOD1) account for 20% of familial ALS (FALS). We report a unique clinicogenotype of a Japanese family with a novel SOD 1 mutation. A 37-year-old woman (the proband) noticed muscle weakness in the left lower limb. Her mother had developed progressive lower motor neuron signs in four extremities at 38 years of age. Subsequently she was diagnosed as ALS and died of respiratory failure at 15 months after clinical onset. Neurological examination of the proband showed absent muscle stretch reflexes in the let knee and the left ankle without Babinski signs. Mild to moderate degree of muscle weakness existed in the left lower extremity. Muscle atrophy was presented in the left thigh. Initial pulmonary function revealed forced vital capacity of 91.1%. Electromyography disclosed ongoing denervation muscle potentials in the left lower extremity. SOD1 analysis demonstrated amino acid substitution of glycine by serine at codon 85 (G85S) in exon 4. Six months later, marked muscle weakness and atrophy expanded to four extremities. All muscle stretch reflexes were absent. Three months later, ventilator support with a tracheostomy was needed. The patient died at 18 months after clinical onset. Clinical hallmarks of this FALS family indicate that G85S mutation of SOD1 may cause rapidly progressive form of pure lower motor neuron signs.