Mutations

PSEN1 V82L

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.22929G>C
Genomic Mutation Name (NT1): g.39483G>C
dbSNP ID: rs63749967
Coding/Non-Coding: Coding
Genomic Region: Exon 4
Mutation Type: Point, Missense
Codon Change: GTG to CTG

Findings

This mutation was originally identified in a French family referred to as "SAL 508". The three affected individuals, across three generations, presented with early-onset Alzheimer’s disease with onset ranging from 53 to 58 years of age. Autosomal-dominant transmission was confirmed by segregation analysis (Campion et al., 1995). This mutation was reported in 1995, the same year that the presenilin-1 gene was cloned (Sherrington et al., 1995).

Neuropathology

Unknown.

Biological Effect

In CHO and HEK-293 cells expressing APP695, the mutation resulted in a slightly lower ratio of secreted Aβ42/Aβ40 (Shioi et al., 2007).

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References

Paper Citations

  1. . Mutations of the presenilin I gene in families with early-onset Alzheimer's disease. Hum Mol Genet. 1995 Dec;4(12):2373-7. PubMed.
  2. . Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature. 1995 Jun 29;375(6534):754-60. PubMed.
  3. . FAD mutants unable to increase neurotoxic Abeta 42 suggest that mutation effects on neurodegeneration may be independent of effects on Abeta. J Neurochem. 2007 May;101(3) Epub 2007 Jan 24 PubMed.

Further Reading

Papers

  1. . Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum Mol Genet. 1998 Jan;7(1):43-51. PubMed.
  2. . Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet. 1999 Sep;65(3):664-70. PubMed.

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Mutations of the presenilin I gene in families with early-onset Alzheimer's disease. Hum Mol Genet. 1995 Dec;4(12):2373-7. PubMed.