Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer’s disease
Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer’s disease
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DOI：
10.1136/jnnp.2003.010611
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发表时间：
2004-06
期刊：
影响因子：
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通讯作者：
Y. Wakutani;K. Watanabe;Y. Adachi;K. Wada-isoe;K. Urakami;Haruaki Ninomiya;T. Saido;T. Hashimoto;T. Iwatsubo;Kenji Nakashima
中科院分区：
文献类型：
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作者：
Y. Wakutani;K. Watanabe;Y. Adachi;K. Wada-isoe;K. Urakami;Haruaki Ninomiya;T. Saido;T. Hashimoto;T. Iwatsubo;Kenji Nakashima
目的：研究日本可能家族性阿尔茨海默病（FAD）谱系中淀粉样蛋白前体蛋白（APP）基因中一个新的错义突变Asp678Asn （D678N）。受试者：先证者是一位72岁的女性。符合阿尔茨海默病可能标准的痴呆症状出现在60岁左右，并在10多年的时间里缓慢恶化，没有明显的脑血管并发症，无论是临床上还是神经影像学上。方法：采用聚合酶链反应单链构象多态性（PCR-SSCP）和序列分析对先证者的基因组DNA进行APP基因外显子16和17突变的检测。结果：先证者APP外显子16分析显示APP基因678密码子GAC核苷酸替换为AAC核苷酸，导致Asp氨基酸替换为Asn （D678N）。APP D678N突变在先证者和失智姐姐中均存在杂合性。结论：突变Abeta （Asn7-Abeta）的产生和积累或D678N突变APP的功能失调可能与该家系阿尔茨海默病的发生有关。
Objective: To describe a novel missense mutation, Asp678Asn (D678N), in the amyloid precursor protein (APP) gene in a Japanese pedigree of probable familial Alzheimer’s disease (FAD). Subject: The proband was a women of 72. Symptoms of dementia that fulfilled the criteria for probable Alzheimer’s disease appeared at about 60 years of age, and slowly worsened over more than 10 years without evident cerebrovascular complications, either clinically or neuroradiologically. Methods: Polymerase chain reaction single strand conformational polymorphism (PCR-SSCP) analysis followed by sequence analysis was used to examine genomic DNA of the proband for mutations in the APP gene exons 16 and 17. Results: Analysis of the APP exon 16 in the proband showed a GAC to AAC nucleotide substitution in codon 678 of the APP gene, causing an amino acid substitution of Asp to Asn (D678N). Heterozygosity of the APP D678N mutation was found in the proband and in the demented elder sister. Conclusions: The production and accumulation of mutated Abeta (Asn7-Abeta) or the misfunction of D678N mutant APP may have pathogenic properties for the development of Alzheimer’s disease in this pedigree.