Mutations

PSEN1 L219P

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73659459 T>C
dbSNP ID: rs63750761
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CTT to CCT
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 7

Findings

This mutation was found in an Australian woman of British ancestry with a family history of dementia, including nine affected relatives spanning five generations (Smith et al., 1999). At 47 years of age, the proband began experiencing memory loss and cognitive impairment, which progressed in a manner consistent with AD, with deficits in orientation, recall, and language.  The mutation was also detected in an affected sister and an affected cousin of the proband, but not in 50 unrelated subjects.

Neuropathology
Neuropathological examination of the brain of the proband’s sister, who carried the mutation and died in a demented state at age 54, confirmed an AD diagnosis according to CERAD criteria. Amyloid plaques and neurofibrillary tangles were widespread, but most concentrated in the hippocampus where they were associated with moderate to severe neuronal loss. In addition, meningeal congophilic amyloid angiopathy was detected in the cortex and cerebellum, with moderate intracortical angiopathy. In the proband, PET and SPECT scans showed hypoperfusion and hypometabolism of the temporal lobes and the right parietal lobe.

Biological Effect
Unknown.

Last Updated: 23 Apr 2019

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References

Paper Citations

  1. . Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the presenilin-1 gene. Neuroreport. 1999 Feb 25;10(3):503-7. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the presenilin-1 gene. Neuroreport. 1999 Feb 25;10(3):503-7. PubMed.

Other mutations at this position

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