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

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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

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Presenilin-1
Dementia
Alzheimer Disease
Mutation
Autopsy
Nucleotides
Chromosomes, Human, Pair 14
Myoclonus
Genetic Heterogeneity
Aphasia
Codon
Seizures
Stroke
Alzheimer's Disease
Onset
Genes
Substitution

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Devi, G., Fotiou, A., Jyrinji, D., Tycko, B., DeArmand, S., Rogaeva, E., ... Mayeux, R. (2000). Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease. Archives of Neurology, 57(10), 1454-1457.

Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease. / Devi, Gayatria; Fotiou, Alexandra; Jyrinji, Darlene; Tycko, Benjamin; DeArmand, Steve; Rogaeva, Ekaterina; Song, You Quiang; Medieros, Helena; Liang, Yan; Orlacchio, Antonio; Williamson, Jennifer; St. George-Hyslop, P.; Mayeux, Richard.

In: Archives of Neurology, Vol. 57, No. 10, 2000, p. 1454-1457.

Research output: Contribution to journalArticle

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 2000, 'Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease', Archives of Neurology, vol. 57, no. 10, pp. 1454-1457.
Devi, Gayatria ; Fotiou, Alexandra ; Jyrinji, Darlene ; Tycko, Benjamin ; DeArmand, Steve ; Rogaeva, Ekaterina ; Song, You Quiang ; Medieros, Helena ; Liang, Yan ; Orlacchio, Antonio ; Williamson, Jennifer ; St. George-Hyslop, P. ; Mayeux, Richard. / Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease. In: Archives of Neurology. 2000 ; Vol. 57, No. 10. pp. 1454-1457.
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