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

Gayatria Devi, Alexandra Fotiou, Darlene Jyrinji, Benjamin Tycko, Steve DeArmand, Ekaterina Rogaeva, You Quiang Song, Helena Medieros, Yan Liang, Antonio Orlacchio, Jennifer Williamson, P. St. George-Hyslop, Richard Mayeux

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1454-1457
Number of pages4
JournalArchives of Neurology
Volume57
Issue number10
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)

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