A novel pathogenic mutation (Leu262Phe) found in the presenilin 1 gene in early-onset Alzheimer's disease.
Several mutations causing early-onset familial Alzheimer's disease (AD) have been detected in the presenilin 1 (PS-1) gene. Pathogenic mutations have also been described in an homologous gene, presenilin 2 (PS-2). In order to screen for mutations in these genes, cDNA samples from early-onset AD cases were analysed, using single strand conformation polymorphism (SSCP) and direct cDNA sequencing. Two missense mutations in the PS-1 gene were detected, a previously unidentified amino acid substitution Leu262Phe and an earlier reported amino acid substitution Glu318Gly. No disease-related mutations were found in the PS-2 gene.
Forsell
C
C
Karolinska Institute, Department of Geriatric Medicine, Huddinge University Hospital, Novum, Sweden.
Froelich
S
S
Axelman
K
K
Vestling
M
M
Cowburn
R F
RF
Lilius
L
L
Johnston
J A
JA
Engvall
B
B
Johansson
K
K
Dahlkild
A
A
Ingelson
M
M
St George-Hyslop
P H
PH
Lannfelt
L
L
D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics*; D019943:Amino Acid Substitution; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007930:Leucine; D008565:Membrane Proteins / Q000235:genetics*; D010649:Phenylalanine; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D053764:Presenilin-1; D053766:Presenilin-2; D017422:Sequence Analysis, DNA
D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D010649:Phenylalanine; D007930:Leucine