Mutations

TREM2 D86V

Overview

Pathogenicity: Frontotemporal Dementia : Unclear Pathogenicity
Clinical Phenotype: Frontotemporal Dementia
Reference Assembly: GRCh37 (105)
Position: Chr6:41129135 A>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GAC to GTC
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 2

Findings

Two Turkish sisters presenting with an FTD-like syndrome and seizures were found to be compound heterozygotes, carrying both the Y38C and D86V variants (Guerreiro et al., 2013). Their mother was a heterozygous carrier of the D86V variant, as was a healthy control in a Turkish cohort previously screened for mutations in TREM2 exon 2 (Guerreiro et al., 2013).

Neuropathology

Unknown. MRI of the proband revealed cortical atrophy that was especially prominent in the frontal, lateral temporal, and parietal lobes; thinning of the corpus callosum; periventricular white-matter abnormalities; ventricular enlargement; and probable calcification in the globus pallidus, similar to what is seen in Nasu-Hakola disease. However, the patient did not show any evidence of bone involvement (Guerreiro et al., 2013).

Biological Effect

The aspartate-to-valine substitution in TREM2 impairs protein maturation and results in decreased cell-surface expression. This variant is apparently unable to undergo complex N-linked glycosylation, but alternatively may undergo O-linked glycosylation (Sirkis et al., 2017).

Last Updated: 07 Feb 2018

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References

Paper Citations

  1. . Novel compound heterozygous mutation in TREM2 found in a Turkish frontotemporal dementia-like family. Neurobiol Aging. 2013 Dec;34(12):2890.e1-5. Epub 2013 Jul 17 PubMed.
  2. . Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol. 2013 Jan;70(1):78-84. PubMed.
  3. . Neurodegeneration-associated mutant TREM2 proteins abortively cycle between the ER and ER-Golgi intermediate compartment. Mol Biol Cell. 2017 Oct 1;28(20):2723-2733. Epub 2017 Aug 2 PubMed.

Other Citations

  1. Y38C

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Novel compound heterozygous mutation in TREM2 found in a Turkish frontotemporal dementia-like family. Neurobiol Aging. 2013 Dec;34(12):2890.e1-5. Epub 2013 Jul 17 PubMed.

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