Mutations

PSEN1 E120D (A>C)

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.25563A>C
Genomic Mutation Name (NT1): g.42117A>C
dbSNP ID: rs63751272
Coding/Non-Coding: Coding
Genomic Region: Exon 5
Mutation Type: Point, Missense
Codon Change: GAA to GAC

Findings

This mutation was described in a British kindred, known as family V. The reported pedigree had ten affected individuals over four generations, four of whom were known to have autopsy-confirmed AD. The average age of onset in this family was 46, and ranged from 41 to 53 years. The mutation was detected in four affected members of the family and in one at risk individual under that age of 50 (Poorkaj et al., 1998).

This mutation was also detected in a French pedigree, known as ALZ 57, with four affected individuals over three generations. In this family onset ranged from 42-53, but clinical details were not reported other than that the family had early-onset AD (Campion et al., 1999).

In a paper attempting to identify patterns of pathology associated with various familial AD mutations, two brain specimens from patients carrying E120D mutations were analyzed, but it was not indicated whether these individuals carried the A>T or A>C transversion. Age of onset in these individuals was recorded as 34 and 53 years and age at death as 51 and 62 years, respectively. Language loss, seizures, and rigidity were noted as clinical features (Mann et al., 2001).

Neuropathology

Unknown.

Biological Effect

Unknown.

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References

Paper Citations

  1. . Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene. Hum Mutat. 1998;11(3):216-21. 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.
  3. . Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin-1-linked Alzheimer's disease. Am J Pathol. 2001 Jun;158(6):2165-75. PubMed.

Further Reading

Papers

  1. . Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update. J Med Genet. 2005 Oct;42(10):793-5. Epub 2005 Jul 20 PubMed.

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene. Hum Mutat. 1998;11(3):216-21. PubMed.

Other mutations at this position

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