Mutations Position Table
PSEN1 A431 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| A431E |
AD : Pathogenic, SP : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 12 | Neuropathology consistent with AD. Widespread white-matter abnormalities in several patients with motor impairments, high incidence of cerebral microhemorrhages. In one case, Lewy body pathology. |
Aβ42/Aβ40 ratio increased in vitro and Aβ (37 + 38 + 40) / (42 + 43) decreased in cultured cells. Toxic peptide Aβ43 was particularly elevated. Increased expression of cell cycle genes and activation of REST in iPSC-neurons. Enhanced MAO-A activity in HT-22 cells. |
Rogaeva et al., 2001; Yescas et al., 2006 |
| A431V |
AD : Likely Pathogenic | Substitution | Substitution | Missense | Coding | Exon 12 | Unknown, but in one case FDG-PET at MCI-AD stage showed low metabolic rates in posterior cingulate gyrus, posterior and lateral parietal cortices, and medial temporal regions; elevated tau and phospho-tau in CSF. |
Unknown. Multiple in silico algorithms predicted damaging. |
Matsushita et al., 2002 |
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