Mutations Position Table
PSEN1 L424 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| L424H |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 12 | Unknown; generalized cerebral atrophy by MRI; diffuse cerebral hypoperfusion by SPECT. |
Increased Aβ42/Aβ40 and Aβ43; decreased Aβ37/Aβ42. |
Raux et al., 2005; Zekanowski et al., 2006 |
| L424P |
AD : Likely Pathogenic | Substitution | Substitution | Missense | Coding | Exon 12 | Unknown, but in proband, MRI showed medial temporal lobe atrophy and global cortical atrophy; PET showed hypometabolism in parietal areas, the precuneus, and the posterior cingulate cortex. Also, reduced CSF Aβ42. |
Unknown, but predicted pathogenic by multiple in silico algorithms. 3D in silico analysis predicted shortening of two intramembrane α-helices and creation of a new one. |
Guven et al., 2019 |
| L424R |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 12 | Unknown; MRI showed cortical and subcortical atrophy with a thin corpus callosum. |
Increased Aβ42/Aβ40 and Aβ43 levels, and decreased Aβ37/Aβ42. |
Kowalska et al., 1999 |
| L424F |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 12 | Unknown, but neuroimaging in two patients revealed brain atrophy with white-matter changes. |
Increased Aβ42/Aβ40 and decreased Aβ37/Aβ42 in cultured cells.
|
Mehrabian et al., 2006 |
| L424V |
AD : Not Classified, Atypical Dementia : Not Classified | Substitution | Substitution | Missense | Coding | Exon 12 | Unknown; CT and SPECT imaging showed diffuse cortical and subcortical atrophy and hypoperfusion affecting the frontal, temporal, and parietal lobes in one patient. In another, fronto-temporal atrophy was predominant, as revelaed by CT and MRI. |
Increased Aβ40, Aβ42, and Aβ42/Aβ40 in vitro. |
Robles et al., 2009 |
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