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 |
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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