The clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients
The clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients
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DOI：
10.1002/ana.410400614
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发表时间：
1996-12-01
影响因子：
11.2
通讯作者：
StGeorgeHyslop, PH
中科院分区：
文献类型：
--
作者：
Ikeda, M;Sharma, V;StGeorgeHyslop, PH
我们报告了早发性家族性阿尔茨海默病（FAD）日本患者早老素I（PS-I）基因两种不同错义突变相关的临床和神经病理表型。在AM/JPN 1家系中，在核苷酸1102处发现错义突变（C->T），预测其导致密码子260处的丙氨酸至缬氨酸错义取代。该家系平均发病年龄40.3岁，病程8-19岁，无明显症状。该家系的3名成员的神经病理学研究显示广泛的老年斑，神经元缠结，神经元丢失，以及丰富的血管周围软膜下淀粉样蛋白沉积在Virchow-Robin空间和Pick样神经元内包涵体在齿状回的存在。在第二个家系中，传递了1027位的C->T核苷酸取代，导致密码子285处丙氨酸错义突变为缬氨酸，该疾病的发病较晚（平均51年），但病程更快。与PS-I外显子9中的其他错义突变相关的疾病表型的比较显示，没有临床或病理表型，其独特地将与PS-I突变相关的阿尔茨海默病与其他形式的早发性PAD区分开，这意味着需要直接突变筛查来识别这些病例。
We report the clinical and neuropathologic phenotypes associated with two different missense mutations in the presenilin I (PS-I) gene in Japanese patients with early-onset familial Alzheimer's disease (FAD). In the AM/JPN1 pedigree a missense mutation (C-->T) was found at nucleotide 1102, which is predicted to cause an alanine-to-valine missense substitution at codon 260. In this family, the disease had a mean age of onset of 40.3 rears and an indolent course (range, 8-19 years). Neuropathologic studies in 3 members of this pedigree showed widespread senile plaques, neuro-fibrillary tangles, and neuronal loss, as well as abundant perivascular subpial amyloid deposits in the Virchow-Robin spaces and the presence of Pick-like intraneuronal inclusions in the dentate gyrus. In the second pedigree, transmitting a C-->T nucleotide substitution at position 1027, leading to the missense mutation of alanine to valine at codon 285, the disease had a later onset (mean, 51 years) but a more rapid course. Comparison of the disease phenotypes associated with other missense mutations in exon 9 of PS-I reveals no clinical or pathological phenotype, which uniquely distinguishes Alzheimer's disease associated with PS-I mutations from other forms of early-onset PAD, implying that direct mutation screening is required to identify these cases.