Mutations

TREM2 W78Ter

Overview

Pathogenicity: Nasu-Hakola Disease : Pathogenic
Clinical Phenotype: Nasu-Hakola Disease
Position: (GRCh38/hg38):Chr6:41161421 G>A
Position: (GRCh37/hg19):Chr6:41129159 G>A
dbSNP ID: rs104893998
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: TGG to TAG
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 2

Findings

The rs104893998 variant introduces a premature stop codon in place of tryptophan at amino acid 78. This variant, in a homozygous state, was found in patients from two Swedish families affected by Nasu-Hakola disease (NHD; also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy) (Paloneva et al., 2002), a rare autosomal recessive disease characterized by bone cysts and early onset frontotemporal dementia (Paloneva et al., 2002). The variant was not found in 100 Caucasian controls (Paloneva et al., 2002).

Neuropathology

Unknown. Brain atrophy was reported in one NHD patient homozygous for this mutation; whether this finding was from autopsy or imaging was not specified (Paloneva et al., 2002).

Biological Effect

This variant is predicted to result in a truncated protein lacking the transmembrane and cytoplasmic domains.

Last Updated: 07 Feb 2023

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References

Paper Citations

  1. Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, Bianchin M, Bird T, Miranda R, Salmaggi A, Tranebjaerg L, Konttinen Y, Peltonen L. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am J Hum Genet. 2002 Sep;71(3):656-62. Epub 2002 Jun 21 PubMed.
  2. Paloneva J, Autti T, Hakola P, Haltia MJ. Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL). In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mefford HC, Stephens K, Amemiya A, Ledbetter N, editors. SourceGeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. 2002 Jan 24 [updated 2015 Mar 12].

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, Bianchin M, Bird T, Miranda R, Salmaggi A, Tranebjaerg L, Konttinen Y, Peltonen L. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am J Hum Genet. 2002 Sep;71(3):656-62. Epub 2002 Jun 21 PubMed.

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