Abe K
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Tohoku J Exp Med. 1997 Apr;181(4):389-409. doi: 10.1620/tjem.181.389.
Clinical and molecular analyses of neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and spinocerebellar ataxia type 1 (SCA1) were performed. In the present study, a Japanese family of AD with an Ala285Val substitution in exon 8 of the presenilin-1 (PS-1) gene was found. This family was characterized by relatively late onset (mean age at 50 years) in familial AD with PS-1 gene mutation and by absence of myoclonus, seizure or paratonia. Magnetic resonance image (MRI) study showed marked linear signal abnormalities in white matter of parietoocctipital lobes, suggesting a presence of cortical amyloid angiopathy of the patient with PS-1 gene mutation. Clinical characteristics of familial amyotrophic lateral sclerosis (FALS) with four different missense point mutations in exons 2, 4, and 5 of the Cu/Zn superoxide dismutase (SOD) gene were reported. Although features of progressive neurogenic muscular atrophy was common in patients of these families, patients of each family showed characteristic clinical features. Although lower motor sign was evident in all cases, hyperreflexia varied from 0 to 100% among patients with the different mutations, and Babinski sign was not observed in any cases. Bulbar palsy was frequent with a mutation, but not present with another mutation. SOD activity of red blood cells was generally reduced with minor variations. CAG trinucleotide repeat expansion was analyzed in 25 families with hereditary ataxia of Menzel type in the northeast of Japan. Twenty of 38 patients in 12 families had expanded allele for spinocerebellar ataxia type 1 (SCA1). Study of the number of CAG repeats in various tissues showed no differences in the repeat length in lymphocytes, muscle or brain; sperm, however, showed an obvious expansion. This may be a clue to a possible mechanism for the molecular basis of paternal anticipation of the disease. These results suggest that clinical features of some familial cases of neurodegenerative diseases such as AD, ALS, and SCA1 are well correlated with their genetic mutations.
对诸如阿尔茨海默病（AD）、肌萎缩侧索硬化症（ALS）和1型脊髓小脑共济失调（SCA1）等神经退行性疾病进行了临床和分子分析。在本研究中，发现了一个日本AD家族，其早老素-1（PS-1）基因第8外显子存在Ala285Val替换。该家族的特征是在伴有PS-1基因突变的家族性AD中发病相对较晚（平均年龄50岁），且无肌阵挛、癫痫发作或紧张性反射。磁共振成像（MRI）研究显示顶枕叶白质有明显的线性信号异常，提示存在PS-1基因突变患者的皮质淀粉样血管病。报道了在铜/锌超氧化物歧化酶（SOD）基因第2、4和5外显子中有四种不同错义点突变的家族性肌萎缩侧索硬化症（FALS）的临床特征。虽然进行性神经源性肌肉萎缩的特征在这些家族的患者中很常见，但每个家族的患者都表现出特征性的临床特征。虽然在所有病例中都明显存在下运动神经元体征，但不同突变患者的腱反射亢进从0%到100%不等，且在任何病例中均未观察到巴宾斯基征。延髓麻痹在一种突变中很常见，但在另一种突变中不存在。红细胞的SOD活性通常降低，但有轻微差异。对日本东北部25个门泽尔型遗传性共济失调家族进行了CAG三核苷酸重复扩增分析。12个家族的38名患者中有20名具有1型脊髓小脑共济失调（SCA1）的扩增等位基因。对各种组织中CAG重复数的研究表明，淋巴细胞、肌肉或大脑中的重复长度没有差异；然而，精子显示出明显的扩增。这可能是该疾病父系遗传早现分子基础的一种可能机制的线索。这些结果表明，AD、ALS和SCA1等一些家族性神经退行性疾病的临床特征与其基因突变密切相关。
