title: Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease.
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. Arch Neurol. 2000;57:1454-1457
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain,The Gertrude Sergievsky Center, Columbia University, New York, NY 10032, USA.
authors.forename: G
authors.initials: G
authors.lastname: Devi
authors.forename: A
authors.initials: A
authors.lastname: Fotiou
authors.forename: D
authors.initials: D
authors.lastname: Jyrinji
authors.forename: B
authors.initials: B
authors.lastname: Tycko
authors.forename: S
authors.initials: S
authors.lastname: DeArmand
authors.forename: E
authors.initials: E
authors.lastname: Rogaeva
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Song
authors.forename: H
authors.initials: H
authors.lastname: Medieros
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: A
authors.initials: A
authors.lastname: Orlacchio
authors.forename: J
authors.initials: J
authors.lastname: Williamson
authors.forename: P
authors.initials: P
authors.lastname: St George-Hyslop
authors.forename: R
authors.initials: R
authors.lastname: Mayeux
mesh_terms: D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D016874:Neurofibrillary Tangles / Q000378:metabolism; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D053764:Presenilin-1
chemical_list: D001057:Apolipoproteins E; D003062:Codon; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1