Mutations Position Table

PSEN2 M239 Mutations

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
M239I
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Moderate cortical atrophy; Numerous neurofibrillary tangles; Numerous senile plaques, especially in the amygdala.

Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF; Reduced calcium release.

rs63749884
Coding
Exon 7
Point, Missense
ATG to ATA
0 Finckh et al., 2000
M239V
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Diffuse cerebral atrophy; Senile plaques; Neurofibrillary tangles (stage VI of Braak and Braak); Ectopic neurons in the subcortical white matter; Extracellular "ghost" neurofibrillary tangles.

Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.

rs28936379
Coding
Exon 7
Point, Missense
ATG to GTG
0 Rogaev et al., 1995

There are two reported variants at codon 239 in the fifth transmembrane domain of PSEN2. These variants result in the replacement of the methionine at this position with either isoleucine or valine. These are rare variants each described in a single kindred, both of which are Italian in origin. These were two of the earliest mutations in PSEN2 to be reported, and both have been shown to segregate with AD in their respective kindreds. In addition both have been shown to produce elevated levels of Aβ42 in vitro and increase the Aβ42/Aβ40 ratio compared to wild-type PSEN2 (Walker et al., 2005).