Mutations

PSEN1 V89L

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.22950G>T
Genomic Mutation Name (NT1): g.39504G>T
dbSNP ID: rs63750815
Coding/Non-Coding: Non-Coding
Genomic Region: Exon 4
Mutation Type: Point, Missense
Codon Change: GTG to TTG

Findings

This is a rare mutation identified in a family from Barcelona, Spain. The reported pedigree included three affected family members over two generations who developed early-onset Alzheimer’s disease. The clinical presentation in this family was notable for early and severe personality changes (e.g. apathy, irritability, paranoia) and early behavioral disturbances prior to cognitive impariment. Age of onset in this family ranged from 46 to 51 years. V89L is considered likely pathogenic due to the presence of the mutation in the proband and an affected sibling and its absence in a healthy sibling. Genetic analysis was not possible in the proband’s affected father as he was predeceased (Queralt et al., 2002; Lleó et al., 2002).

Neuropathology

Postmortem analysis of the proband’s brain confirmed the AD diagnosis. Neurofibrillary tangles and neuritic plaques with dystrophic neurites corresponding to stage VI of Braak and Braak were observed. Plaques were common in the hippocampus, amygdala, and neocortex. Tangles were most abundant in the neocortex and hippocampus, but also found in the striatum, thalamus, and midbrain. Blood vessels in the cortex showed signs of amyloid angiopathy. Overall, the brain showed moderate cortical atrophy and enlarged ventricles (Queralt et al., 2002).

Biological Effect

Unknown.

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References

Paper Citations

  1. . A novel mutation (V89L) in the presenilin 1 gene in a family with early onset Alzheimer's disease and marked behavioural disturbances. J Neurol Neurosurg Psychiatry. 2002 Feb;72(2):266-9. PubMed.
  2. . Frequency of mutations in the presenilin and amyloid precursor protein genes in early-onset Alzheimer disease in Spain. Arch Neurol. 2002 Nov;59(11):1759-63. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . A novel mutation (V89L) in the presenilin 1 gene in a family with early onset Alzheimer's disease and marked behavioural disturbances. J Neurol Neurosurg Psychiatry. 2002 Feb;72(2):266-9. PubMed.