Mutations Position Table

PSEN1 R278 Mutations

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Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
R278K
Alzheimer's Disease, Spastic Paraparesis Alzheimer's Disease : Not Classified, Spastic Paraparesis : Not Classified

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
Alzheimer's Disease, Spastic Paraparesis Alzheimer's Disease : Not Classified

Neuropathology consistent with AD was detected in one brain biopsy.

Unknown, but multiple in silico algorithms predicted it is damaging.

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 : Not Classified

Neuropathology consistent with AD in two cases; with more Aβ deposition in the APOE3/4 carrier than the APOE2/3 carrier. Also, in the amygdala, α-synuclein pathology in both cases, and, in one case, TDP-43 pathology. 

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
Alzheimer's Disease, Spastic Paraparesis Alzheimer's Disease : Not Classified

Unknown

Unknown, but multiple in silico algorithms predicted it is damaging.

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

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