Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease
Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease
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DOI：
10.1001/archneur.57.10.1454
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发表时间：
2000-10-01
影响因子：
--
通讯作者：
Mayeux, R
中科院分区：
文献类型：
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作者：
Devi, G;Fotiou, A;Mayeux, R
一名早发性、尸检证实的阿尔茨海默病（AD）成人的两个孩子在20多岁时发生痴呆，随后发现14号染色体上早老素1（PS1）基因的密码子434发生了新的突变，1548位核苷酸发生了G → T置换，1549位核苷酸发生了C → G置换。2名儿童中年龄较小的儿童在尸检时确诊为AD。这3例患者的病程特征为发病后5年内出现认知和行为问题，伴肌阵挛、癫痫发作和失语。两名祖父母在78岁和66岁时临床诊断为AD伴中风，但都没有PS1突变。没有其他活着的家庭成员患有痴呆症，也没有任何其他家庭成员有PS1突变。我们得出结论，先证者的受影响的父母可能是PS1中这些never突变的最近创始人。该家族表现出AD的临床和遗传异质性。
Two children of an adult with early-onset, autopsy-confirmed Alzheimer disease (AD) developed dementia in their late 20s and mere subsequently found to have novel mutations in codon 434 of the presenilin 1 (PS1) gene on chromosome 14, a G-to-T substitution at nucleotide 1548 and a C-to-G substitution at nucleotide 1549. The younger of the 2 children had AD confirmed at postmortem examination. The disease course in these 3 individuals was characterized by cognitive and behavioral problems accompanied by myoclonus, seizures, and aphasia within 5 years after onset. Two grandparents had clinically diagnosed AD with stroke beginning at ages 78 and 66 years, but neither had a PS1 mutation. No other living family member tvas demented, nor did any other family member have the PS1 mutation. We conclude that the affected parent of the proband was a likely recent founder for these never mutations in PS1. The family demonstrates the clinical and genetic heterogeneity of AD.