Mutations

PSEN1 L219F

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73659458 C>T
dbSNP ID: rs63749987
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CTT to TTT
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 7

Findings

This mutation was identified in a member of an Italian family with early onset AD (Terreni et al., 2000). The proband's APP gene was also screened, and no additional mutations were found.

Neuropathology
Unknown.

Biological Effect
An in vitro assay using purified proteins to test the ability of this mutant to cleave the APP-C99 substrate revealed it produces less Aβ40 and more Aβ42 than wildtype PSEN1, resulting in an elevated Aβ42/Aβ40 ratio (Sun et al., 2017).

Last Updated: 26 Apr 2019

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References

Paper Citations

  1. . A novel missense mutation (L219F) in exon 8 of the presenilin 1 gene in an Italian family with presenile familial Alzheimer's disease. Neurobiol Aging. 2000 May-Jun;21(Suppl 1):176-7.
  2. . Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E476-E485. Epub 2016 Dec 5 PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . A novel missense mutation (L219F) in exon 8 of the presenilin 1 gene in an Italian family with presenile familial Alzheimer's disease. Neurobiol Aging. 2000 May-Jun;21(Suppl 1):176-7.

Other mutations at this position

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