Mutations Position Table
PSEN1 I143 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| I143M |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Neuropathology consistent with AD in one case. |
Unknown, but other mutations at this location alter Aβ peptide production and, in wild-type PSEN1, I143 forms part of the substrate-binding pore.
|
Heckmann et al., 2002 |
| I143N |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown |
Increased Aβ42/Aβ40 and decreased Aβ37/Aβ42 in cultured cells. |
Raux et al., 2005 |
| I143T |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Neuropathology consistent with AD. |
Increased the Aβ42/Aβ40 ratio and decreased the Aβ (37 + 38 + 40) / (42 + 43) and Aβ37/Aβ42 ratios. |
Cruts et al., 1995; Rogaeva et al., 2001 |
| I143V |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 5 | Neuropathology consistent with AD, including abundant amyloid plaques and severe neurofibrillary tangle pathology (stage VI Braak and Braak). Amyloid deposits were comprised largely of Aβ42, with little to no Aβ40. There was minimal amyloid angiopathy in vessels. |
Increased Aβ42 and Aβ42/Aβ40 ratio in cells and in vitro. |
Gallo et al., 2011 |
| I143F |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Neuropathology consistent with AD, but in one case, more widespread distribution of plaques in the temporal sulcus compared with sporadic AD, and lower ratio of Ab40 to Ab42/Ab43 in plaques. Also, accelerated NFT formation and neuronal loss. |
Increased Aβ42/Aβ40 and decreased Aβ (37 + 38 + 40) / (42 + 43) and Aβ37/Aβ42 indicating a deleterious effect.
|
Rossor et al., 1996; Palmer et al., 1999 |
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