Mutations

PSEN1 N32N

Overview

Pathogenicity: Alzheimer's Disease : Likely Benign
Clinical Phenotype: Alzheimer's Disease, None
Reference Assembly: GRCh37/hg19
Position: Chr14:73637513 T>C
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Silent
Codon Change: AAT to AAC
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 4

Findings

This is a silent polymorphism, considered most likely not pathogenic. It was first reported in a Caucasian woman from northern Italy who was diagnosed with probable Alzheimer’s disease according to NINCDS-ADRDA criteria. She experienced symptom onset at age 81 and did not have a family history of dementia, consistent with sporadic AD. Segregation analysis was not possible in this case. The T>C polymorphism was absent in 114 healthy unrelated individuals, but the reporting authors indicated that the polymorphism was most likely not pathogenic due to the fact that it was a synonymous change and in a position not conserved in PSEN2 or in other species (Scacchi et al., 2007).

Consistent with this proposal, the variant was described as "most likely benign" or causing an "only small increase in risk" based on its allele count (12) and frequency (0.0043 percent) in the gnomAD variant database (Koriath et al., 2018). The penetrance was calculated to be two percent or less. Hsu and colleagues classified this variant as "not pathogenic" (Hsu et al., 2020)

Neuropathology

Unknown.

Biological Effect

Unknown.

Last Updated: 07 Oct 2021

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

  1. . A mutation screening by DHPLC of PSEN1 and APP genes reveals no significant variation associated with the sporadic late-onset form of Alzheimer's disease. Neurosci Lett. 2007 May 18;418(3):282-5. Epub 2007 Mar 21 PubMed.
  2. . Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series. Mol Psychiatry. 2018 Oct 2; PubMed.
  3. . Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2. Neurobiol Dis. 2020 Jun;139:104817. Epub 2020 Feb 19 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . A mutation screening by DHPLC of PSEN1 and APP genes reveals no significant variation associated with the sporadic late-onset form of Alzheimer's disease. Neurosci Lett. 2007 May 18;418(3):282-5. Epub 2007 Mar 21 PubMed.

Alzpedia

Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.