Mutations

PSEN2 Q228L

Overview

Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr1:227076646 A>T
dbSNP ID: rs63750880
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CAG to CTG
Reference Isoform: PSEN2 isoform 1 (448 aa)
Genomic Region: Exon 7

Findings

This variant was identified in a Polish patient. The proband was diagnosed with MCI at the time of the study. Cognitive symptoms surfaced at the age of 60 and included irritability and insomnia, along with mild deficits in memory and short episodes of disorientation. The proband had a positive family history of dementia. Her mother was diagnosed with probable AD at age 80. Segregation could not be assessed.

The variant was absent in 100 unrelated Polish patients with sporadic AD and 100 unrelated age-matched healthy controls (Zekanowski et al., 2003). However, it was identified in the gnomAD variant database and described as most likely having reduced penetrance, with an allele count of two, and a frequency of 0.0008 percent (Koriath et al., 2018).

Neuropathology

Unknown.

Biological Effect

Unknown. The substitution affects a residue in transmembrane domain V, which is conserved in PSEN1.

Last Updated: 19 Jul 2019

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References

Paper Citations

  1. . Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. Exp Neurol. 2003 Dec;184(2):991-6. PubMed.
  2. . 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

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. Exp Neurol. 2003 Dec;184(2):991-6. PubMed.

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