Mutations

PSEN2 M174V

Overview

Pathogenicity: Alzheimer's Disease : Not Pathogenic
Clinical Phenotype: Alzheimer's Disease, None
Genomic Mutation Name (MET1): g.6206A>G
Genomic Mutation Name (NT1): g.22541A>G
dbSNP ID:
Coding/Non-Coding: Coding
Genomic Region: Exon 6
Mutation Type: Point, Missense
Codon Change: ATG to GTG

Findings

This mutation was first reported in 2008, but further details were not available (Clarimón et al., 2008; Andreoli et al., 2008).

Subsequently, the mutation was reported in a woman who developed Alzheimer’s disease at age 54. Due to a lack of family history and the fact that this residue is not conserved between PSEN1 and PSEN2, M174V was categorized by the authors as possibly pathogenic (Guerreiro et al., 2010).

A later study found M174V in a family with a history of late onset AD, but the mutation did not segregate with disease. Specifically, it was detected in one affected individual and three healthy family members. In addition, some affected members of the family were not carriers, arguing against pathogenicity (Cruchaga et al., 2012).

Neuropathology

Atrophy in both parietal regions and hypoperfusion in temporoparietal regions was seen in one affected mutation carrier (Guerreiro et al., 2010).

Biological Effect

M174V is located in the third transmembrane domain of PSEN2. The residue is not conserved in PSEN1. The functional effects of this residue change are unknown, but it is predicted “benign” by PolyPhen2 (Cruchaga et al., 2012).

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References

Paper Citations

  1. . Genetic screening in a large cohort of early-onset Alzheimer's disease patients from Spain: novel mutations in the amyloid precursor protein and presenilines. . Alzheimer's & Dementia 4 Supp 2: T583, 2008
  2. . Gene symbol: PSEN2. Disease: Alzheimer disease. Hum Genet. 2008 Oct;124(3):304. PubMed.
  3. . 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.
  4. . Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. PLoS One. 2012;7(2):e31039. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Gene symbol: PSEN2. Disease: Alzheimer disease. Hum Genet. 2008 Oct;124(3):304. PubMed.
  2. . Genetic screening in a large cohort of early-onset Alzheimer's disease patients from Spain: novel mutations in the amyloid precursor protein and presenilines. . Alzheimer's & Dementia 4 Supp 2: T583, 2008
  3. . 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.