Mutations

PSEN2 T301M

Overview

Pathogenicity: Alzheimer's Disease : Benign
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr1:227078994 C>T
dbSNP ID: rs144277432
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ACG to ATG
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 10

Findings

This PSEN2 variant was reported in an individual from the Netherlands who died with a clinical diagnosis of Alzheimer's disease. He first began to experience deficits in short- and long-term memory around age 60. His condition gradually deteriorated and he died approximately 10 years after symptom onset. He had a positive family history of dementia. Several family members were reportedly affected by dementia syndromes; however, details were not reported and segregation with disease was not assessed (Croes et al., 2004).

Sixteen heterozygotes, most of non-Finnish European ancestry, were reported in the gnomAD variant database (v2.1.1, Nov 2021).

Neuropathology

Unknown.

Biological Effect

In vitro, introduction of this mutant form of presenilin-2 did not alter the ratio of secreted Aβ42/Aβ40 (Croes et al., 2004). Moreover, this variant's PHRED-scaled CADD score was 19.9, just below the commonly used threshold of 20 to predict deleteriousness (CADD v.1.6, Nov 2021). 

Last Updated: 09 Nov 2021

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References

Paper Citations

  1. . Octapeptide repeat insertions in the prion protein gene and early onset dementia. J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1166-70. PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Octapeptide repeat insertions in the prion protein gene and early onset dementia. J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1166-70. PubMed.

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