Mutations

PSEN2 T122P

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.3636A>C
Genomic Mutation Name (NT1): g.19974A>C
dbSNP ID: rs63749851
Coding/Non-Coding: Coding
Genomic Region: Exon 5
Mutation Type: Point, Missense
Codon Change: ACG to CCG

Findings

This mutation was first identified in a patient diagnosed with probable early-onset Alzheimer's disease. The patient, who was identified as "Patient 6" in the study, was from Germany and had a positive family history of dementia. Her mother and maternal grandmother died at 48 and 51 years old, respectively. The patient had disease onset at age 46 (Finckh et al., 2000).

This mutation was identified in a second, presumably unrelated, German patient who also had a family history of dementia. The patient, identified as "P. 48", had disease onset at age 50. The patient's father and paternal uncle also had been diagnosed with dementia (Finckh et al., 2005).

Neuropathology

Unknown.

Biological Effect

When transfected into fibroblasts lacking endogenous PSEN1 or PSEN2, the T122P mutation 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, the T122P mutation produced elevated levels of Aβ42 and increased the Aβ42/Aβ40 ratio (Walker et al., 2005).

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References

Mutations Citations

  1. APP KM670/671NL (Swedish)

Paper Citations

  1. . High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000 Jan;66(1):110-7. PubMed.
  2. . Novel mutations and repeated findings of mutations in familial Alzheimer disease. Neurogenetics. 2005 May;6(2):85-9. Epub 2005 Mar 18 PubMed.
  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. . High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000 Jan;66(1):110-7. PubMed.

Other mutations at this position

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