Mutations

PSEN1 S212Y

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.44654C>A
Genomic Mutation Name (NT1): g.61260C>A
dbSNP ID:
Coding/Non-Coding: Coding
Genomic Region: Exon 7
Mutation Type: Point, Missense
Codon Change: TCC to TAC

Findings

This mutation was identified in a family with multiple affected family members. The proband was a Caucasian female with a history of memory problems beginning at age 38. She experienced progressive impairment and was diagnosed with dementia at the age of 44. At 55, she was still in a relatively mild stage of dementia, but activities of daily living were affected.

Her father had died at the age of 70 with a progressive dementia syndrome with onset around age 56. Details of his condition or prior family history were not known.

Of the proband’s three siblings, two were affected. Onset in these siblings occurred at ages 41 and 44, with death of both reported at age 55. One of these siblings had autopsy-confirmed AD and was a mutation carrier. The genotype of the other affected sibling is not known. A 66-year-old sister was unaffected and did not carry the mutation. Therefore, segregation analysis suggests that the mutation segregates with disease in this family (Ringman et al., 2011).

Neuropathology

One family member had autopsy-confirmed AD with neurofibrillary tangle pathology (Braak stage VI) and frequent neuritic plaques. Severe amyloid angiopathy was noted in the cerebellum and occipital cortex, and α-synuclein pathology was detected in the amygdala (Ringman et al., 2011).

Biological Effect

When expressed in HEK293 cells expressing APP with the Swedish mutation, mutant PSEN1 increased Aβ40, Aβ42, and the Aβ40/Aβ42 ratio compared with cells expressing wild-type PSEN1 (Ringman et al., 2011).

Comments

Make a Comment

To make a comment you must login or register.

Comments on this content

No Available Comments

References

Mutations Citations

  1. APP KM670/671NL (Swedish)

Paper Citations

  1. . Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation. Neurosci Lett. 2011 Jan 10;487(3):287-92. Epub 2010 Nov 19 PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation. Neurosci Lett. 2011 Jan 10;487(3):287-92. Epub 2010 Nov 19 PubMed.