Mutations
PSEN1 N32N
Quick Links
Overview
Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity
Clinical Phenotype: Alzheimer's Disease, None
Reference Assembly: GRCh37 (105)
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.
Neuropathology
Unknown.
Biological Effect
Unknown.
Last Updated: 16 Jul 2019
References
Paper Citations
- Scacchi R, Gambina G, Moretto G, Corbo RM. 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.
- Koriath C, Kenny J, Adamson G, Druyeh R, Taylor W, Beck J, Quinn L, Mok TH, Dimitriadis A, Norsworthy P, Bass N, Carter J, Walker Z, Kipps C, Coulthard E, Polke JM, Bernal-Quiros M, Denning N, Thomas R, Raybould R, Williams J, Mummery CJ, Wild EJ, Houlden H, Tabrizi SJ, Rossor MN, Hummerich H, Warren JD, Rowe JB, Rohrer JD, Schott JM, Fox NC, Collinge J, Mead S. 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.
Further Reading
Learn More
Protein Diagram
Primary Papers
- Scacchi R, Gambina G, Moretto G, Corbo RM. 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.
Comments
No Available Comments
Make a Comment
To make a comment you must login or register.