Molecular evidence of presenilin 1 mutation in familial early onset dementia.
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.
Matsubara-Tsutsui
Miho
M
Department of Geriatric Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsengun, Ehime, Japan.
Yasuda
Minoru
M
Yamagata
Hidehisa
H
Nomura
Takuo
T
Taguchi
Keiko
K
Kohara
Katsuhiko
K
Miyoshi
Koho
K
Miki
Tetsuro
T
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
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D004247:DNA