Mutations Position Table

PSEN1 R278 Mutations

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
R278K
Spastic Paraparesis, Alzheimer's Disease Alzheimer's Disease : Pathogenic, Spastic Paraparesis : Pathogenic

Unknown; MRI and CT scans reported as normal in one individual

Increased Aβ42 production in patient fibroblasts; but reduced Aβ42 and Aβ40 production in assay with purified proteins. In both cases, increased Aβ42/Aβ40.

rs63749891
Coding
Exon 8
Point, Missense
AGA to AAA
0 Assini et al., 2003
R278T
Spastic Paraparesis, Alzheimer's Disease Alzheimer's Disease : Pathogenic

Neuropathology consistent with AD was detected in one brain biopsy.

Unknown

rs63749891
Coding
Exon 8
Point, Missense
AGA to ACA
0 Kwok et al., 1997
R278I
Alzheimer's Disease, Progressive Nonfluent Aphasia Alzheimer's Disease : Pathogenic, Progressive Nonfluent Aphasia : Pathogenic

Unknown; MRI showed multiple white-matter foci; Atrophy minimal or absent.

Deficient maturation of mutant protein in iPSC-derived neurons. Selective increase in secreted Aβ43; impaired endoproteolysis of PSEN1. Increased Aβ42/Aβ40, Aβ42/Aβ38, and particularly Aβ43/Aβ40 ratios. Aβ38/Aβ40 ratio similar to wild-type.  Impaired processing of the ApoER2 LDL receptor. 

 

rs63749891
Coding
Exon 8
Point, Missense
AGA to ATA
1 Godbolt et al., 2004
R278S
Spastic Paraparesis, Alzheimer's Disease Alzheimer's Disease : Pathogenic

Unknown

Unknown

rs63750524
Coding
Exon 8
Point, Missense
AGA to AGC
0 Raman et al., 2007

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