Mutations Position Table
PSEN1 Y159 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| Y159C |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown, but in one case, MRI revealed diffuse parietal and hippocampal atrophy, and FDG-PET showed severe hypometabolism in bilateral frontoparieto-temporal cortex. |
Unknown, but in silico algorithms predicted probably damaging (Polyphen2) and not tolerated (SIFT). Cryo-EM suggests structural role in PSEN1-APP interaction. CADD score = 28.3. |
Kim et al., 2020 |
| Y159F |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown, but CSF biomarkers suggestive of AD. |
Increased Aβ2 resulting in an increased Aβ42/Aβ40 ratio in cells. |
Kerchner and Holbrook, 2012 |
| Y159S |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown, but MRI in one patient revealed mild atrophy of the temporal and parietal lobes, and the hippocampus. |
Decreased Aβ40 and moderately increased Aβ42, resulting in a 4-fold increase in the Aβ42/Aβ40 ratio in cells. |
Li et al., 2022 |
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