Mutations

PSEN1 M84T

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73637668 M>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ATG to ACG
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 4

Findings

This mutation was identified in a screen of patients with early onset AD from 28 French hospitals (Lanoiselée et al., 2017). Families were included when at least two first-degree relatives, spanning two generations, suffered from early onset AD with an age of onset of 65 years or younger. Age at onset in this pedigree, which included three affected individuals, ranged from 52 to 60 years, and disease duration ranged from two to seven years. The clinical presentation was mainly progressive cognitive decline. The mutation was identified in two affected family members, and was absent from the exome database ExAC which includes ~60,000 controls.

Neuropathology
Neuropathological examination of the proband showed global atrophy, particularly in the temporal lobes. In addition, samples from the cerebellum and the frontal, temporal, and parietal cortices showed numerous senile plaques and neurofibrillary tangles associated with severe cerebral amyloid angiopathy. No Lewy bodies were observed.

Biological Effect
The biological effect of this mutation is unknown, but another mutation at this site, PSEN1 M84V, was reported to co-segregate with AD and alter Aβ peptide production. Moreover, the site is conserved between PSEN1 and PSEN2.

Based on the pathogenicity criteria developed by Guerreiro and colleagues (Guerreiro et al., 2010), this mutation was classified as definitely pathogenic (Lanoiselée et al., 2017).

Last Updated: 31 May 2019

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Mutations Citations

  1. PSEN1 M84V

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

Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.