Mutations

PSEN1 G111W

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73637748 G>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GGG to TGG
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 4

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 47, and a disease duration of 4 years. The carrier was homozygous for the APOE 3 allele. 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
Unknown.

Biological Effect
Unknown.

Another mutation at this site, PSEN1 G111V, was also found in an individual with early onset AD and was reported to alter Aβ production in transfected cells. 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: 02 Jul 2019

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References

Mutations Citations

  1. PSEN1 G111V

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.

Other Citations

  1. Lanoiselée et al., 2017

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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