A further presenilin 1 mutation in the exon 8 cluster in familial Alzheimer's disease.
Recent studies suggest that mutations in the presenilin 1 gene, which encodes a polypeptide predicted to be a multispanning membrane protein, are responsible for the majority of cases of early onset, autosomal dominant Alzheimer's disease. Here we describe a further mutation in the presenilin 1 gene (R269G) in a family with early onset Alzheimer's disease. This mutation is in exon 8 which appears to be a favoured region for pathogenic mutations. In the presenilin protein the region coded for by this exon is likely to comprise a domain located on the membrane surface. We discuss the likely effects of the exon 8 mutations on the structure of the exon and in the pathogenesis of the disease.
Suncoast Alzheimer's Disease Laboratories, Department of Psychiatry, University of South Florida, Tampa 33613, USA.
J
J
Perez-Tur
R
R
Croxton
K
K
Wright
H
H
Phillips
C
C
Zehr
R
R
Crook
M
M
Hutton
J
J
Hardy
E
E
Karran
G W
GW
Roberts
S
S
Lancaster
T
T
Haltia
D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D005091:Exons; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D053764:Presenilin-1
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1