Mutations Position Table
PSEN1 P117 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| P117L |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Neuropathology consistent with AD. Unusually high amyloid burden, especially in the molecular layer of the cerebellum and in cerebellar vessels. |
Increased Aβ42/40 ratio and decreased Aβ37/40, Aβ37/42, and Aβ38/42 ratios in cells; reduced ε-cleavage; Aβ49→Aβ46 and Aβ43→Aβ40 trimming. In addition, inhibited neurite outgrowth and neurofilament assembly, increased cell-cycle arrest, and decreased neuronal differentiation of progenitor cells. |
Wisniewski et al., 1998 |
| P117Q |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown, but CSF biomarkers (Aβ42, tau, and phospho-tau) were in the AD pathological range in one case. |
Unknown, but multiple in silico algorithms predicted a damaging effect. |
Lanoiselée et al., 2017 |
| P117R |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown. |
Increased Aβ42/40 ratio and decreased Aβ37/40, Aβ37/42, and Aβ38/42 ratios in cells, indicating reduced γ-processivity. Also, affected cell cycle in immortalized patient lymphocytes. |
Zekanowski et al., 2003 |
| P117A |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown. |
Increased Aβ42/40 and Aβ42/Aβ total ratios and decreased Aβ37/40, Aβ37/42, and Aβ38/42 ratios. |
Anheim et al., 2007 |
| P117S |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Neuropathology consistent with AD according to CERAD criteria; Neuronal loss estimated to be greater than 70 percent in one brain; extensive loss of white matter; active gliosis throughout the brain; Lewy bodies. |
Increased Aβ42/40 ratio and decreased Aβ37/40, Aβ37/42, and Aβ38/42 ratios in transfected cells, indicating reduced γ-processivity. Increased production of Aβ42 and Aβ43 at the expense of Aβ37 and Aβ40; Aβ38 was only moderately decreased. Reduced neurite outgrowth.
|
Dowjat et al., 2004 |
| P117T |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown |
Unknown, but 5 in silico algorithms predicted damaging. PHRED-CADD score: 26.5 |
Jia et al., 2020 |
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