Mutations Position Table
APP T714 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| T714A (Iranian) |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 17 | Progressive cortical atrophy; White matter lesions. |
Increased longer Aβ peptides: Aβ42, Aβ46, Aβ48. Increased Aβ38+Aβ42+Aβ45+Aβ48; decreased Aβ40+Aβ43+Aβ46+Aβ49. |
Pasalar et al., 2002 |
| T714I (Austrian) |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 17 | Extensive neuronal loss; Diffuse gliosis; Neurofibrillary tangles; Amyloid plaques including diffuse "cloudy" plaques. |
Increased Aβ42/Aβ40 and Aβ38/Aβ40 ratios, increased Aβ48 → Aβ45 → Aβ42 → Aβ38 pathway; decreased Aβ49 → Aβ46 → Aβ43 → Aβ40 pathway. Inefficient processing of Aβ; increased levels of membrane-anchored Aβ48. |
Kumar-Singh et al., 2000 |
The two pathogenic mutations at codon 714 are located at a primary site of γ-secretase cleavage and sit just outside the C-terminal of the Aβ sequence. Like other mutations in this region of APP, they are thought to alter APP processing such that more Aβ42 is produced. The clinical picture for these two mutations differs, especially with respect to average age of onset. The T714I mutation appears to cause a more aggressive form of the disease than the T714A mutation with an earlier age of onset and more rapid progression.
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