Mutations

PSEN1 A285S

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr14:73664822 G>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GCT to TCT
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 8

Findings

This mutation was identified in a Korean woman with AD and a family history of the disease (Kim et al., 2020). Her symptoms, starting at age 54, included memory impairment, acalculia, delusion, depression, and anxiety. Disease duration was five years. Her APOE genotype was APOE3/APOE3.

This variant was not found in the gnomAD database, nor in 500 Korean controls.

Neuropathology
Neuropathological data are unavailable, but MRI revealed bilateral hippocampal atrophy, and FDG-PET showed bilateral hypometabolism in the temporal cortex. In addition, she tested amyloid-positive as assessed by PiB-PET.

Biological Effect
The biological effect of this mutation is unknown, but the site is evolutionarily conserved (GERP score = 5.82). Several in silico algorithms (SIFT, Polyphen-2, LRT, MutationTaster, MutationAssessor, FATHMM, PROVEAN, CADD, REVEL, and Reve in the VarCards database) predicted this variant is damaging (Xiao et al., 2021). Kim and colleagues reported predictions of probably damaging (Polyphen 2) and tolerable (SIFT), and a CADD score of 25.9 (Kim et al., 2020). 

Last Updated: 13 Sep 2021

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References

Paper Citations

  1. . PSEN1 variants in Korean patients with clinically suspicious early-onset familial Alzheimer's disease. Sci Rep. 2020 Feb 26;10(1):3480. PubMed.
  2. . APP, PSEN1, and PSEN2 Variants in Alzheimer's Disease: Systematic Re-evaluation According to ACMG Guidelines. Front Aging Neurosci. 2021;13:695808. Epub 2021 Jun 18 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . PSEN1 variants in Korean patients with clinically suspicious early-onset familial Alzheimer's disease. Sci Rep. 2020 Feb 26;10(1):3480. PubMed.

Other mutations at this position

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