Mutations

PSEN1 Q222P

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73659468 A>C
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CAG to CCG
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 7

Findings

This mutation was first identified in a woman who developed memory impairment with word-finding difficulties and dyscalculia at age 46 (Scahill et al., 2013Ryan et al., 2016). She was adopted and had no information about her birth family. The mutation was also reported in an individual who developed dementia at age 49 (Koriath et al., 2018). The mutation was absent from 100 healthy individuals (Ryan et al, 2016), and from the ExAC exome database (Koriath et al., 2018).

Neuropathology

Unknown

Biological Effect

The residue is conserved between species and PSENs, and other pathogenic mutations have been reported at this site. The variant was predicted to be probably damaging by Polyphen and deleterious by Provean (Ryan et al., 2016). Ryan and colleagues classified it as probably pathogenic.

Last Updated: 30 May 2019

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References

Paper Citations

  1. . Genetic Influences on Atrophy Patterns in Familial Alzheimer's Disease: A Comparison of APP and PSEN1 Mutations. J Alzheimers Dis. 2013 Jan 1;35(1):199-212. PubMed.
  2. . Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer's disease: a case series. Lancet Neurol. 2016 Dec;15(13):1326-1335. Epub 2016 Oct 21 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. . Genetic Influences on Atrophy Patterns in Familial Alzheimer's Disease: A Comparison of APP and PSEN1 Mutations. J Alzheimers Dis. 2013 Jan 1;35(1):199-212. PubMed.
  2. . Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer's disease: a case series. Lancet Neurol. 2016 Dec;15(13):1326-1335. Epub 2016 Oct 21 PubMed.

Other mutations at this position

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