Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease

被引:33
作者
Devi, G
Fotiou, A
Jyrinji, D
Tycko, B
DeArmand, S
Rogaeva, E
Song, YQ
Medieros, H
Liang, Y
Orlacchio, A
Williamson, J
St George-Hyslop, P
Mayeux, R
机构
[1] Columbia Univ, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, Dept Neurol, New York, NY 10032 USA
[2] Columbia Univ, Dept Pathol, New York, NY 10032 USA
[3] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA
[4] Columbia Univ, Dept Psychiat, New York, NY 10032 USA
[5] Long Isl Alzheimers Dis Assistence Ctr, Stony Brook, NY USA
[6] Univ Rochester, Dept Psychiat, Rochester, NY USA
[7] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA
[8] Toronto Western Hosp, Dept Med, Div Neurol, Toronto, ON M5T 2S8, Canada
[9] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada
[10] Lenox Hill Hosp, New York Memory & Hlth Aging Serv, New York, NY 10021 USA
[11] Lenox Hill Hosp, Dept Med, Div Neurol, New York, NY 10021 USA
[12] Lenox Hill Hosp, Dept Psychiat, New York, NY 10021 USA
关键词
D O I
10.1001/archneur.57.10.1454
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
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页码:1454 / 1457
页数:4
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