Mutations

PSEN1 V96F

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73637703 G>T
dbSNP ID: rs63750601
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GTC to TTC
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 4

Findings

This rare mutation was identified in a single Japanese family. The reported pedigree consisted of four affected family members over three generations. All affected individuals had early onset Alzheimer’s disease, with a mean age at onset of 52.5 ± 5.07 years (range: 49 to 60 years). The mutation was not found in unaffected family members or in 100 control individuals (Kamino et al., 1996).

Neuropathology

Unknown.

Biological Effect

In vitro studies revealed a robust decrease in Aβ42 and Aβ40 production, as well as drastically reduced autoproteolytic endopeptidase activity (Brunkan et al., 2005; Sun et al., 2017). 

Last Updated: 25 Jul 2019

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References

Paper Citations

  1. . Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families. Neurosci Lett. 1996 Apr 26;208(3):195-8. PubMed.
  2. . Two domains within the first putative transmembrane domain of presenilin 1 differentially influence presenilinase and gamma-secretase activity. J Neurochem. 2005 Sep;94(5):1315-28. PubMed.
  3. . Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E476-E485. Epub 2016 Dec 5 PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families. Neurosci Lett. 1996 Apr 26;208(3):195-8. PubMed.

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