Mutations

PSEN1 A164V

Overview

Pathogenicity: Alzheimer's Disease : Likely Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr14:73653571 C>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GCC to GTC
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 6

Findings

This mutation was described in a 75-year-old man who met NINCDS-ADRDA criteria for probable AD (Roeber et al., 2015). In addition to memory problems, his symptoms included language and speech impairments, and motor symptoms including dysphagia, spasticity, brisk reflexes, and recurrent falls. The patient had a positive family history for dementia, but specifics were not reported.

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

Neuropathology

Unknown. Cerebral MRI showed generalized atrophy of the brain with pronounced involvement of the anterior temporal lobe, including the hippocampus.

Biological Effect

Unknown. Several in silico algorithms (SIFT, Polyphen-2, LRT, MutationTaster, MutationAssessor, FATHMM, PROVEAN, CADD, REVEL, and Reve in the VarCards database) predicted this variant is damaging (Roeber et al., 2015Xiao et al., 2021).

Last Updated: 03 Aug 2021

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References

Paper Citations

  1. . Three novel presenilin 1 mutations marking the wide spectrum of age at onset and clinical patterns in familial Alzheimer's disease. J Neural Transm (Vienna). 2015 Dec;122(12):1715-9. Epub 2015 Sep 8 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,

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Three novel presenilin 1 mutations marking the wide spectrum of age at onset and clinical patterns in familial Alzheimer's disease. J Neural Transm (Vienna). 2015 Dec;122(12):1715-9. Epub 2015 Sep 8 PubMed.

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