Mutations Position Table
PSEN1 L424 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.