Mutations

PSEN1 P117Q

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73640285 C>A
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CCA to CAA
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 5

Findings

This mutation was identified in a French study that screened 129 individuals with sporadic AD diagnosed according to the National Institute of Aging–Alzheimer’s Association criteria with an age at onset below 51 (Lanoiselée et al., 2017). The mutation carrier had progressive cognitive decline beginning at age 37, and a disease duration of two years. The carrier had APOE2 and APOE3 alleles. Examination of parental DNA indicated the mutation arose de novo. The mutation was absent from the exome database ExAC, including approximately 60,000 controls.

Neuropathology
No neuropathological data were available, but levels of Ab42, tau, and phospho-tau in the mutation carrier’s cerebrospinal fluid were in the AD pathological range (587 pg/ml; >1,200 pg/ml; and 173 pg/ml, respectively).

Biological effect
The biological effect of this mutation is unknown, but four other mutations associated with AD have been reported at this site, affecting Ab peptide levels and various cellular functions.
Based on the pathogenicity criteria developed by Guerreiro and colleagues (Guerreiro et al., 2010), this mutation was classified as probably pathogenic (Lanoiselée et al., 2017).

Last Updated: 01 Jun 2019

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References

Paper Citations

  1. . APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med. 2017 Mar;14(3):e1002270. Epub 2017 Mar 28 PubMed.
  2. . Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010 May;31(5):725-31. Epub 2008 Jul 30 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med. 2017 Mar;14(3):e1002270. Epub 2017 Mar 28 PubMed.

Other mutations at this position

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