Mutations

PSEN1 L250F

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr14:73659553 G>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: TTG to TTT
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 7

Findings

This mutation was found in a large North American Aboriginal kindred with early onset familial AD (Butler et al., 2010). In contrast to previously reported families with PSEN1 L250 mutations, the 16 affected members of this kindred did not present with either myoclonus or seizures. The mutation segregated with disease as revealed by its presence in six affected individuals and its absence from two unaffected individuals who were past the median age of onset. It was also absent from the gnomAD variant database (gnomAD v2.1.1, July 2021).

Neuropathology

Nueropathology data were unavailable, but CT scans from six affected individuals showed frontal, parietal, and temporal atrophy.

Biological Effect

Unknown, but 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).

Last Updated: 24 Aug 2021

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

  1. . A novel PS1 gene mutation in a large Aboriginal kindred. Can J Neurol Sci. 2010 May;37(3):359-64. 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. . A novel PS1 gene mutation in a large Aboriginal kindred. Can J Neurol Sci. 2010 May;37(3):359-64. PubMed.

Other mutations at this position

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.