Mutations

PSEN2 V393M

Overview

Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.12205G>A
Genomic Mutation Name (NT1): g.28540G>A
dbSNP ID:
Coding/Non-Coding: Coding
Genomic Region: Exon 11
Mutation Type: Point, Missense
Codon Change: GTG to ATG

Findings

This mutation was first identified in a Danish patient with progressive language and memory disturbances that began at age 50. The proband was diagnosed with Alzheimer's disease due to profound impairment of episodic memory, but also had severe language impairment early in the course of the disease, which is atypical for AD. There was a family history of dementia, but it was not possible to determine segregation. The mutation was absent in 13 unaffected family members and in one family member with late-onset AD. It was also absent in 384 normal controls (Lindquist et al., 2008; Lindquist et al., 2009).

Neuropathology

Unknown. FDG-PET imaging of the proband showed bilateral hypometabolism in the parieto-occipital regions (Lindquist et al., 2008).

Biological Effect

This mutation results in an amino acid change from valine to methionine within transmembrane domain VIII. In vitro, expression in HEK-293 cells showed no change in secreted Aβ42 or the Aβ42/Aβ40 ratio, suggesting V393M may be a benign variant rather than pathogenic (Lindquist et al., 2008).

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References

Paper Citations

  1. . A novel presenilin 2 mutation (V393M) in early-onset dementia with profound language impairment. Eur J Neurol. 2008 Oct;15(10):1135-9. Epub 2008 Aug 22 PubMed.
  2. . Genetic testing in familial AD and FTD: mutation and phenotype spectrum in a Danish cohort. Clin Genet. 2009 Aug;76(2):205-9. Epub 2009 Jul 29 PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . A novel presenilin 2 mutation (V393M) in early-onset dementia with profound language impairment. Eur J Neurol. 2008 Oct;15(10):1135-9. Epub 2008 Aug 22 PubMed.