Mutations

PSEN2 N141D

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr1:227073303 A>G
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: AAC to GAC
Reference Isoform: PSEN2 isoform 1 (448 aa)
Genomic Region: Exon 5

Findings

This mutation was found in a Han Chinese individual diagnosed with probable AD according to the NINCDS-ADRDA and DSM-IV criteria (Wang et al., 2019).  The patient did not have a family history of AD and was APOE4 negative. Age at onset was 59 years.

Neuropathology
Unknown

Biological Effect
This mutation was predicted to be damaging by three algorithms with a PHRED CADD score of 24.9. Other mutations at this position, N141I and N141Y, have been linked to AD and N141I produced elevated levels of Aβ42 and increased the Aβ42/Aβ40 ratio (Walker et al., 2005). The mutation was described as definitely pathogenic based on the Guerreiro et al., 2010 guidelines (Wang et al., 2019).

Last Updated: 30 Oct 2019

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References

Mutations Citations

  1. PSEN2 N141I (Volga German)
  2. PSEN2 N141Y

Paper Citations

  1. . Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer's disease. J Psychiatr Res. 2019 Jun;113:141-147. Epub 2019 Mar 30 PubMed.
  2. . Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios. J Neurochem. 2005 Jan;92(2):294-301. PubMed.
  3. . 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.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer's disease. J Psychiatr Res. 2019 Jun;113:141-147. Epub 2019 Mar 30 PubMed.

Other mutations at this position

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