Novel Presenilin 1 Mutations Associated With Early Onset of Dementia in a Family With Both Early-Onset and Late-Onset Alzheimer Disease
Authors:
- Alexandra FotiouAFAlexandra Fotiou
- Darlene JyrinjiDJDarlene Jyrinji
- Benjamin TyckoBTBenjamin Tycko
- Steve DeArmandSDSteve DeArmand
- Ekaterina RogaevaEREkaterina Rogaeva
- You-Quiang SongYou-Quiang Song
- Helena MedierosHMHelena Medieros
- Yan LiangYLYan Liang
- Antonio OrlacchioAntonio Orlacchio
- Jennifer WilliamsonJWJennifer Williamson
- Peter St George-HyslopPeter St George-Hyslop
Open Access
- 1 October 2000
- journal article
- case report
- Published by American Medical Association (AMA) in Archives of Neurology
- Vol. 57 (10) , 1454-1457
Abstract
Two children of an adult with early-onset, autopsy-confirmed Alzheimer disease (AD) developed dementia in their late 20s and were 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 was 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 novel mutations in PS1. The family demonstrates the clinical and genetic heterogeneity of AD.Keywords
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