Mutations

PSEN2 T153S

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
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 6

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
The biological effects of this variant are unknown, but its PHRED-scaled CADD score, which integrates diverse information in silico, was above 20, suggesting a deleterious effect (CADD v.1.6, Nov 2021). Perrone and colleagues suggested classifying this variant as "likely pathogenic" based on their findings of altered Aβ peptides in CSF, particularly Aβ43 (Perrone et al., 2020). However, functional assays to directly determine the variant's biological effects are lacking.

Last Updated: 04 Nov 2021

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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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