Mutations

PSEN2 V150M

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr1:227073330 G>A
dbSNP ID: rs866044092
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GTG to ATG
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 6

Findings

This mutation was found in a screen of APP, PSEN1, and PSEN2 genes of 148 Chinese patients with familial Alzheimer’s disease who had at least two first-degree relatives with dementia (Gao et al., 2019). The carrier of this mutation was a 69-year-old man who suffered from memory loss and disorientation, with symptoms starting at 64 years of age. He was homozygous for the APOE3 allele. A single heterozygote of African/African American ancestry was reported in the gnomAD variant database (v2.1.1, Nov 2021).

Neuropathology
Unknown.

Biological Effect
The biological effect of this mutation is unknown, but orthologous sequence alignments revealed V150 is an evolutionarily conserved residue. In addition, in silico algorithms predicted the mutation to be possibly damaging (PolyPhen), affecting protein function (SIFT), and disease-causing (MutationTaster), with a CADD score of 23.1 (Gao et al., 2019). These authors classified the mutation as “probably pathogenic,” following the algorithm by Guerreiro et al., 2010.

Last Updated: 04 Nov 2021

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References

Paper Citations

  1. . Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease. Neurobiol Aging. 2019 May;77:154-157. Epub 2019 Jan 31 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.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease. Neurobiol Aging. 2019 May;77:154-157. Epub 2019 Jan 31 PubMed.

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