Mutations Position Table

PSEN1 L282 Mutations

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
L282F
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Unknown; MRI showed mild medial temporal atrophy. FDG-PET showed glucose hypometabolism in the bilateral parietal cortices and posterior cingulate gyri.

Unknown.


Coding
Exon 8
Point, Missense
CTT to TTT
0 Hamaguchi et al., 2009
L282P
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Unknown, but in one patient, MRI revealed mild, diffuse cortical atrophy, and FDG-PET showed severe, bilateral hypometabolism in parietal and temporal cortices.

Unknown, but in silico algorithms predicted probably damaging (Polyphen2) and not tolerated (SIFT). CADD score = 28.5


Coding
Exon 8
Point, Missense
CTT to CCT
0 Kim et al., 2020
L282R
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Neuropathology consistent with Alzheimer's disease.

Decreased Aβ42 and obliterated Aβ40 production in vitro.

rs63750050
Coding
Exon 8
Point, Missense
CTT to CGT
0 Aldudo et al., 1998
L282V
Alzheimer's Disease, Cerebral Amyloid Angiopathy Alzheimer's Disease : Pathogenic

Extensive neurofibrillary tangles and amyloid deposits including both dense-cored plaques and diffuse plaques. Severe cerebral amyloid angiopathy (CAA) in the neocortex, hippocampus, and cerebellum. CAA deposits associated with dystrophic neurites and inflammatory gliosis. Severe white-matter loss. Cerebellar amyloid pathology associated with severe CAA and loss of Purkinje cells.

A twofold increase in the Aβ42/Aβ40 ratio compared with cells expressing wild-type PSEN1. In vitro, Aβ42 and Aβ40 production, as well as Aβ42/Aβ40 ratio, similar to wild-type. Impairs trafficking of the APOE receptor apoER2.

rs63749937
Coding
Exon 8
Point, Missense
CTT to GTT
0 Dermaut et al., 2001

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