Mutations

PSEN1 R220P

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr14:73659462 G>C
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CGA to CCA
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 7

Findings

This PSEN1 mutation was found in a Caucasian woman from Italy who met clinical criteria for probable Alzheimer’s disease (Piccoli et al., 2016). Her symptoms started at age 67 with depression and apathy, followed closely by deficits in attention and memory. Later, she also developed a slight ataxic gait. She had a family history of dementia: Her mother developed AD at the age of 68 and died at age 82. Segregation with disease could not be determined.

This variant was absent from the gnomAD variant database (gnomAD v2.1.1, July 2021).

Neuropathology

Unknown. MRI showed diffuse cortico-subcortical cerebral atrophy with multiple foci in the deep white matter.

Biological Effect

The biological effect of this variant is unknown. Although some in silico algorithms to predict the effects of this variant on protein function yielded conflicting results (Piccoli et al., 2016, Xiao et al., 2021), the CADD-PHRED tool, which integrates diverse information, gave it a high deleteriousness score above 20 (CADD v.1.6, Sep 2021).

Last Updated: 21 Sep 2021

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References

Paper Citations

  1. . Novel PSEN1 mutations (H214N and R220P) associated with familial Alzheimer's disease identified by targeted exome sequencing. Neurobiol Aging. 2016 Apr;40:192.e7-11. Epub 2016 Feb 28 PubMed.
  2. . APP, PSEN1, and PSEN2 Variants in Alzheimer's Disease: Systematic Re-evaluation According to ACMG Guidelines. Front Aging Neurosci. 2021;13:695808. Epub 2021 Jun 18 PubMed.

External Citations

  1. gnomAD v2.1.1
  2. CADD v.1.6

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Novel PSEN1 mutations (H214N and R220P) associated with familial Alzheimer's disease identified by targeted exome sequencing. Neurobiol Aging. 2016 Apr;40:192.e7-11. Epub 2016 Feb 28 PubMed.

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