Mutations Position Table
PSEN1 A246 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| A246E |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 7 | Generalized atrophy, most prominently in the frontal lobes and hippocampus. Neuronal loss, gliosis, neurofibrillary tangles, and plaques. |
Increased Aβ42 and Aβ43 secretion, Aβ42/Aβ40 ratio, Aβ42/Aβ total ratio. Decreased production of Aβ40 and Aβ42 in vitro. Disrupts endosomes via accumulation of APP β-CTF. Impaired neuronal differentiation, neural precursor proliferation, viability, autophagy, mitophagy, lysosomal function, ER calcium flux. |
Sherrington et al., 1995 |
| A246P |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 7 | Neuropathology consistent with AD (Braak and Braak stage VI, CERAD C) as well as cerebral amyloid angiopathy. Some α-synuclein inclusions were observed in the entorhinal cortex. Aβ42, tau, and phospho-tau levels in CSF consistent with AD |
Unknown; predicted probably damaging in silico. |
Roeber et al., 2015 |
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