Mutations

PSEN1 Q222R

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73659468 A>G
dbSNP ID: rs63750009
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CAG to CGG
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 7

Findings

This mutation was found in a screen for variants in the open reading frame of the PSEN1 gene in participants from the United States, Germany, and Canada who had been referred for AD diagnostic testing (Rogaeva et al., 2001). The cohort included 372 patients with AD and 42 asymptomatic individuals with a strong family history of AD. In one family, the Q222R mutation was reported to co-segregate with AD in more than one individual.

Neuropathology
Unknown

Biological Effect
An in vitro assay using purified proteins to test its ability to cleave the APP-C99 substrate revealed it generates more Aβ40 and Aβ42 than wildtype PSEN1, resulting in a modestly elevated Aβ42/Aβ40 ratio (Sun et al., 2017).

Last Updated: 23 Sep 2019

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References

Paper Citations

  1. . Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. 2001 Aug 28;57(4):621-5. PubMed.
  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

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. 2001 Aug 28;57(4):621-5. PubMed.

Other mutations at this position

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