Mutations Position Table
PSEN1 G417 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| G417A |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 12 | Unknown, but MRI and PET are consistent with AD in one case. PiB-PET showed diffuse amyloid in the cerebellum, and the frontal, parietal, and temporal cortices. |
Unknown, but in silico analyses predict mutation is damaging (PolyPhen2, SIFT, Provean). Changes in amino acid bulkiness, polarity, and hydrophobicity, together with 3D modeling, suggest reduced flexibility in transmembrane helix. Splicing may also be affected. |
Giau et al., 2018 |
| G417S |
AD : Not Classified, SP : , Parkinsonism : | Substitution | Substitution | Missense | Coding | Exon 12 | Cotton wool plaques throughout cortex, abundant Aβ deposits in cerebellum and spinal gray matter (one patient). Also, CAA, extensive neuronal loss, astrocytic and microglial markers, and extensive distribution of neocortical Lewy bodies. TDP-43 inclusions in limbic region and temporal cortex. |
Increased Aβ42 and the Aβ42/Aβ40 ratio in cultured cells. |
Miki et al., 2019 |
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.