Mutations

PSEN1 L424V

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic, Atypical Dementia : Pathogenic
Clinical Phenotype: Atypical Dementia
Genomic Mutation Name (MET1): g.71074C>G
Genomic Mutation Name (NT1): g.87685C>G
dbSNP ID:
Coding/Non-Coding: Coding
Genomic Region: Exon 12
Mutation Type: Point, Missense
Codon Change: CTC to GTC

Findings

This mutation was documented in a young woman presenting with an early onset dementia syndrome with a complex clinical phenotype. At the age of 26 she developed symptoms of anorexia nervosa, followed by memory and attention deficits by age 30. Four years later she had developed changes in personality and behavior, including impulsivity and aggression. Her condition deteriorated, and she developed aphasia, stereotyped behaviors, myoclonus, and seizures. Possible diagnoses of Huntington's disease and sporadic Creutzfeldt-Jakob disease were considered and excluded. Her symptoms were indicative of frontal dysfunction reminiscent of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). No family members were affected by early onset dementia, although her maternal grandfather developed dementia after age 80. Segregation of the mutation with disease could not be assessed, but it was absent in 178 unrelated individuals (Robles et al., 2009).

Neuropathology

Unknown. CT and SPECT imaging showed diffuse cortical and subcortical atrophy as well as hypoperfusion affecting the frontal, temporal, and parietal lobes.

Biological Effect

Unknown.

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References

Paper Citations

  1. . Clinical picture of a patient with a novel PSEN1 mutation (L424V). Am J Alzheimers Dis Other Demen. 2009 Feb-Mar;24(1):40-5. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Clinical picture of a patient with a novel PSEN1 mutation (L424V). Am J Alzheimers Dis Other Demen. 2009 Feb-Mar;24(1):40-5. PubMed.

Other mutations at this position

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