Mutations

PSEN1 I439S

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73685909 T>G
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ATC to AGC
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 12

Findings

This mutation was identified in a man who developed memory deficits at approximately 55 years of age and had a family history of early cognitive decline (Gómez-Tortosa et al., 2010). Two years after onset, the man showed deficits in executive functions, praxis, and verbal memory. He also had apathy and depression, as well as moderate levels of anxiety and irritability. The same mutation was found in an affected second-cousin with onset of dementia in his 50s. In addition, four affected women in previous generations died between 58 and 70 years of age after approximately a decade of cognitive deterioration.

Neuropathology
The neuropathology associated with this mutation is unknown. MRI showed diffuse cortical atrophy in the proband.

Biological Effect
PolyPhen analysis predicted the mutation to be “possibly damaging” to PSEN1 function.

Last Updated: 27 Mar 2019

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References

Paper Citations

  1. . Clinical-genetic correlations in familial Alzheimer's disease caused by presenilin 1 mutations. J Alzheimers Dis. 2010;19(3):873-84. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . Clinical-genetic correlations in familial Alzheimer's disease caused by presenilin 1 mutations. J Alzheimers Dis. 2010;19(3):873-84. PubMed.

Other mutations at this position

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