Mutations

PSEN1 A285S

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
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) and another mutation tied to AD, A285V, has been reported at this site. Although the in silico algorithm SIFT predicted it is tolerable, Polyphen2 predicted it is probably damaging. The mutation’s CADD score is 25.9, suggesting it is in the top 1 percent of deleterious variants. The authors classified this mutation as likely pathogenic.

Last Updated: 09 Mar 2020

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References

Mutations Citations

  1. PSEN1 A285V

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.

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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