Mutations Position Table

PSEN1 G417 Mutations

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
G417A
Alzheimer's Disease, Parkinsonism Alzheimer's Disease : Pathogenic

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.


Coding
Exon 12
Point, Missense
GGT to GCT
0 Giau et al., 2018
G417S
Alzheimer's Disease Alzheimer's Disease : Pathogenic, Spastic Paraparesis : Pathogenic

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.

Unknown


Coding
Exon 12
Point, Missense
GGT to AGT
0 Miki et al., 2019

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