Mutations Position Table
PSEN1 R278 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| R278S |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 8 | Unknown |
Unknown, but multiple in silico algorithms predicted it is damaging. |
Raman et al., 2007 |
| R278K |
AD : Not Classified, SP : Not Classified | Substitution | Substitution | Missense | Coding | Exon 8 | 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. |
Assini et al., 2003 |
| R278T |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 8 | Neuropathology consistent with AD was detected in one brain biopsy. |
Increased Aβ42/Aβ40 ratio and decreased Aβ (37 + 38 + 40) / (42 + 43) and Aβ37/Aβ42 ratios in cells. Also, increased Aβ43 levels 10-fold. |
Kwok et al., 1997 |
| R278I |
AD : Pathogenic, Progressive Nonfluent Aphasia : Not Classified | Substitution | Substitution | Missense | Coding | Exon 8 | 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.
|
Godbolt et al., 2004 |
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