title: Molecular evidence of presenilin 1 mutation in familial early onset dementia.
abstract: Early onset familial Alzheimer disease (FAD) has been associated with mutations in three genes, of which presenilin 1 (PSEN1) mutations are the most frequent. We reported previously a variant form of FAD, due to deletion of exon 9 of PSEN1, with spastic paralysis and rigidity. We describe a novel PSEN1 mutation in a family of Japanese origin with six affected individuals of both genders in two generations. The disease is characterized by presenile dementia, which is preceded by spastic paraparesis and apraxia. This mutation, which is predicted to cause a missense substitution of serine for glycine, occurred at codon 266 in exon 8 of PSEN1. The mutation was not found in 200 controls and 200 sporadic AD patients. On this basis alone, it seems this mutation is pathogenic. Our findings provide a new clue to the etiology of the familial early onset dementia.
authors.affiliation: Department of Geriatric Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsengun, Ehime, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Matsubara-Tsutsui
authors.forename: Minoru
authors.initials: M
authors.lastname: Yasuda
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Yamagata
authors.forename: Takuo
authors.initials: T
authors.lastname: Nomura
authors.forename: Keiko
authors.initials: K
authors.lastname: Taguchi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.forename: Koho
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
mesh_terms: D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D053764:Presenilin-1; D017386:Sequence Homology, Amino Acid
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D004247:DNA