Mutations

PSEN1 E280K

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73664807 G>A
dbSNP ID: NA
Coding/Non-Coding: Coding
Genomic Region: Exon 8
Mutation Type: Point, Missense
Codon Change: GAA to AAA

Findings

This mutation was identified in three Malaysian siblings whose family was affected by familial early onset Alzheimer’s disease with prominent behavioral changes and atypical features (Ch’ng et al., 2015). The reported five-generation pedigree shows seven family members with dementia, behavioral change (e.g., aggression), and parkinsonism. The female proband developed symptoms at age 48, starting with mood and behavior changes. She also presented with visual and auditory hallucinations and myclonic jerks. Two of her siblings were also affected by dementia with behavioral changes (onset at age 55 and 57, respectively). Their father had dementia when he died of cancer at age 71. The mutation segregated with disease: it was present in the three affected siblings and absent in 10 unaffected family members.

Neuropathology

Unknown. MRI of the proband showed generalized brain atrophy including atrophy of the hippocampus.

Biological Effect

Unknown. In silico analysis predicted this mutation to be damaging.

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References

Paper Citations

  1. . Identification of two novel mutations, PSEN1 E280K and PRNP G127S, in a Malaysian family. Neuropsychiatr Dis Treat. 2015;11:2315-22. Epub 2015 Sep 8 PubMed.

Further Reading

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Primary Papers

  1. . Identification of two novel mutations, PSEN1 E280K and PRNP G127S, in a Malaysian family. Neuropsychiatr Dis Treat. 2015;11:2315-22. Epub 2015 Sep 8 PubMed.

Other mutations at this position

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