Mutations

PSEN1 E120K

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.25561G>A
Genomic Mutation Name (NT1): g.42115G>A
dbSNP ID: rs63750800
Coding/Non-Coding: Coding
Genomic Region: Exon 5
Mutation Type: Point, Missense
Codon Change: GAA to AAA

Findings

This mutation has been reported in two families. One family of British/Irish decent, known as F121, had six affected family members over three generations. Onset of symptoms ranged from 32 to 39 years in this family, and a diagnosis of AD was confirmed by pathology in some family members (Hutton et al., 1996).

The details of the second family are limited, but the index patient was of Danish origin and developed symptoms at age 43 and had AD with spastic paraparesis. The mean age of onset in this family was reported as 44 years, ranging from 43 to 45 years; however it was unclear how many individuals were affected and segregation with disease could not be assessed due to lack of DNA from individuals other than the index patient (Lindquist et al., 2009).

Neuropathology

Neuropathology consistent with AD (Hutton et al., 1996).

Biological Effect

In vitro this mutation has been shown to increase the Aβ42/Aβtotal ratio when expressed in COS-1 cells cotransfected with APP695 (Murayama et al., 1999).

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References

Paper Citations

  1. . Complete analysis of the presenilin 1 gene in early onset Alzheimer's disease. Neuroreport. 1996 Feb 29;7(3):801-5. 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.
  3. . Enhancement of amyloid beta 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease. Neurosci Lett. 1999 Apr 9;265(1):61-3. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Complete analysis of the presenilin 1 gene in early onset Alzheimer's disease. Neuroreport. 1996 Feb 29;7(3):801-5. PubMed.

Other mutations at this position

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