Mutations

PSEN2 K161R

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr1:227073364 A>G
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: AAG to AGG
Reference Isoform: PSEN2 isoform 1 (448 aa)
Genomic Region: Exon 5

Findings

This mutation was found in a large French study reporting 56 new families with autosomal-dominant early onset Alzheimer’s disease. All probands met NINCDS-ADRDA criteria for probable AD and had a family history of disease (Wallon et al., 2012).

The K161R mutation was detected in one individual in a family with three additional affected individuals. Only the genotype of the proband is known, so segregation with disease could not be determined. Age of onset in this family ranged from 61 to 69 years, with a seven- to 16-year clinical disease course. The mutation was classified as possibly pathogenic according to the algorithm proposed by Guerreiro et al., 2010. A subsequent study reported the variant most likely has reduced penetrance, with an allele count of three, and a frequency of 0.0011 percent in the gnomAD variant database (Koriath et al., 2018).

Neuropathology

Unknown.

Biological Effect

Unknown.

Last Updated: 19 Jul 2019

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References

Paper Citations

  1. . The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers. J Alzheimers Dis. 2012 Jan 1;30(4):847-56. PubMed.
  2. . Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010 May;31(5):725-31. Epub 2008 Jul 30 PubMed.
  3. . 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

No Available Further Reading

Protein Diagram

Primary Papers

  1. . The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers. J Alzheimers Dis. 2012 Jan 1;30(4):847-56. PubMed.

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