Mutations

PSEN2 V148I

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.3714G>A
Genomic Mutation Name (NT1): g.20052G>A
dbSNP ID: rs63750812
Coding/Non-Coding: Coding
Genomic Region: Exon 5
Mutation Type: Point, Missense
Codon Change: GTC to ATC

Findings

This mutation was the third mutation in PSEN2 to be reported. It was identified in a single Spanish individual diagnosed with late-onset Alzheimer's disease. The patient developed symptoms at age 76. There was a positive family history for dementia, but details were not available and segregation could not be assessed (Lao et al., 1998). This mutation was also reported in Beyer et al., 1998.

Neuropathology

Unknown.

Biological Effect

When transfected into fibroblasts lacking endogenous PSEN1 and PSEN2, the V148I variant did not affect steady-state levels of the proteolytic products PSEN2-CTF and PSEN2-NTF compared to wild-type PSEN2. When cotransfected with APP carrying the Swedish mutation, V148I PSEN2 did not affect Aβ42 levels or the Aβ42/Aβ40 ratio (Walker et al., 2005).

 

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References

Paper Citations

  1. . A novel mutation in the predicted TM2 domain of the presenilin 2 gene in a Spanish patient with late-onset Alzheimer's disease. Neurogenetics. 1998 Aug;1(4):293-6. PubMed.
  2. . Identification of a novel mutation (V148I) in the TM2 domain of the presenilin 2 gene in a patient with late-onset Alzheimer disease. Neurobiology of Aging 19 Supp 4: S87, 1998
  3. . Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios. J Neurochem. 2005 Jan;92(2):294-301. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . A novel mutation in the predicted TM2 domain of the presenilin 2 gene in a Spanish patient with late-onset Alzheimer's disease. Neurogenetics. 1998 Aug;1(4):293-6. PubMed.