Mutations

PSEN2 S175C

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.6210C>G
Genomic Mutation Name (NT1): g.22545C>G
dbSNP ID:
Coding/Non-Coding: Coding
Genomic Region: Exon 6
Mutation Type: Point, Missense
Codon Change: TCT to TGT

Findings

This mutation was identified in an Italian kindred. The proband developed insidious memory loss at age 60, followed by progressive dementia and the diagnosis of probable Alzheimer's disease. There was a family history of dementia; the proband's mother had experienced dementia at age 60, and two of the mother's siblings had memory disturbances before the age of 65. The proband had two affected siblings who also carried the mutation. For the three siblings, the mean age of onset was 63 years.  In addition to progressive memory decline, the clinical course in the siblings was characterized by mood changes (primarily depression and apathy), and the proband experienced extrapyramidal signs, namely rigidity and bradykinesia. The mode of inheritance was consistent with autosomal-dominant transmission with high penetrance. The mutation was absent in 247 unrelated individuals (117 healthy controls and 130 individuals with AD) (Piscopo et al., 2010).

Neuropathology

Unknown; MRI of the proband's brain showed focal atrophy in the medial temporal lobe; SPECT showed bilateral hypoperfusion in temporo-parietal regions (Piscopo et al., 2010).

Biological Effect

Unknown. This mutation leads to a subsitution of a residue in the third transmembrane domain of PSEN2.

 

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References

Paper Citations

  1. . A novel mutation in the predicted TMIII domain of the PSEN2 gene in an Italian pedigree with atypical Alzheimer's disease. J Alzheimers Dis. 2010;20(1):43-7. PubMed.

Further Reading

Papers

  1. . A novel Italian presenilin 2 mutation (S175Y). Alzheimer's & Dementia 4 Supp 2: T595, 2008

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . A novel mutation in the predicted TMIII domain of the PSEN2 gene in an Italian pedigree with atypical Alzheimer's disease. J Alzheimers Dis. 2010;20(1):43-7. PubMed.