Mutations

PSEN1 L392P

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr14:73683879 T>C
dbSNP ID: rs63750218
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CTG to CCG
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 11

Findings

This mutation was found in an Italian man with a family history of AD with psychiatric symptoms (Tedde et al., 2000). In four family members, spanning three generations, disease onset was characterized by bipolar affective symptoms and mild memory loss occurring, on average, at 38 years of age. The mutation was present in the proband and absent from 50 unrelated subjects, as well as from the gnomAD variant database (gnomAD v2.1.1, August 2021).

Neuropathology
Neuropathological data are unavailable, but MRI revealed moderate atrophy of the temporal lobes in a symptomatic family member.

Biological Effect
The biological effect of this mutation is unknown, but a pathogenic mutation affecting the same residue, L392V, has been reported and 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 (Xiao et al., 2021). Moreover, L392 is in a domain that binds several proteins, including β-catenin and neuronal plakophilin-related armadillo protein/δ-catenin (Tedde et al., 2000). 

Last Updated: 14 Sep 2021

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Mutations Citations

  1. PSEN1 L392V

Paper Citations

  1. Tedde A, Forleo P, Nacmias B, Piccini C, Bracco L, Piacentini S, Sorbi S. A presenilin-1 mutation (Leu392Pro) in a familial AD kindred with psychiatric symptoms at onset. Neurology. 2000 Nov 28;55(10):1590-1. PubMed.
  2. Xiao X, Liu H, Liu X, Zhang W, Zhang S, Jiao B. 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

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. Tedde A, Forleo P, Nacmias B, Piccini C, Bracco L, Piacentini S, Sorbi S. A presenilin-1 mutation (Leu392Pro) in a familial AD kindred with psychiatric symptoms at onset. Neurology. 2000 Nov 28;55(10):1590-1. PubMed.

Other mutations at this position

View Table

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.