Mutations

PSEN2 T153S

Overview

Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr1:227073340 C>G
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ACC to AGC
Reference Isoform: PSEN2 isoform 1 (448 aa)
Genomic Region: Exon 5

Findings

This variant was found in a study that screened the APP, PSEN1, and PSEN2 genes in 1,431 Alzheimer’s disease (AD) patients from the Belgian neurology consortium BELNEU (Perrone et al., 2020). The authors used a targeted re-sequencing gene panel and selected non-synonymous variants with a minor allele frequency of less than 1 percent.

The carrier of this variant suffered from early onset Alzheimer’s disease and was homozygous for the APOE3 allele. The variant was absent from the gnomAD variant database.

Neuropathology
Neuropathological data are unavailable, but the carrier had reduced levels of Aβ43 and Aβ42 in cerebrospinal fluid (CSF), similar to those observed in carriers of known pathogenic mutations. In addition, Aβ40, sAPPα, and sAPPβ were also reduced. Tau and phospho-tau levels, however, were within the normal range. 

Biological Effect
As noted above, the carrier of this variant had reduced CSF levels of several APP peptides, in particular Aβ43 and Aβ42.

Last Updated: 27 Oct 2020

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References

Paper Citations

  1. . Amyloid-β1-43 cerebrospinal fluid levels and the interpretation of APP, PSEN1 and PSEN2 mutations. Alzheimers Res Ther. 2020 Sep 11;12(1):108. PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Amyloid-β1-43 cerebrospinal fluid levels and the interpretation of APP, PSEN1 and PSEN2 mutations. Alzheimers Res Ther. 2020 Sep 11;12(1):108. PubMed.

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