Mutations

TREM2 A28V

Overview

Pathogenicity: Alzheimer's Disease : Not Pathogenic, Frontotemporal Dementia : Unclear Pathogenicity
Clinical Phenotype: Primary Progressive Aphasia, Progressive Nonfluent Aphasia
Reference Assembly: GRCh37 (105)
Position: Chr6:41129309 C>T
dbSNP ID: rs2234252
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GCG to GTG
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 2

Findings

The A28V variant was found in one Alzheimer’s patient in a Caucasian cohort from the Alzheimer’s Disease Sequencing Project (2927 AD, 2633 cognitively healthy controls) (Sirkis et al., 2016). Subsequently, the variant was not associated with AD in a case-control study of more than 33,000 Caucasian subjects (approximately 18,000 AD and 16,000 controls; odds ratio: 2.56, p = 0.3) (Sims et al., 2017).

The A28V variant was also found in a Spanish patient affected with frontotemporal dementia (primary progressive aphasia, non-fluent variant) (Thelen et al., 2014).

Neuropathology

No data.

Biological Effect

The A28 variant underwent normal maturation but showed increased cell-surface expression when heterologously expressed in HEK293 cells (Sirkis et al., 2016).

 

 

Last Updated: 07 Feb 2018

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References

Paper Citations

  1. . Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression. Acta Neuropathol Commun. 2016 Sep 2;4(1):98. PubMed.
  2. . Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet. 2017 Sep;49(9):1373-1384. Epub 2017 Jul 17 PubMed.
  3. . Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes. Neurobiol Aging. 2014 Nov;35(11):2657.e13-2657.e19. Epub 2014 Jun 20 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet. 2017 Sep;49(9):1373-1384. Epub 2017 Jul 17 PubMed.

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