Mutations

TREM2 W44X

Overview

Pathogenicity: Nasu-Hakola Disease : Pathogenic
Clinical Phenotype: Nasu-Hakola Disease
Reference Assembly: GRCh37 (105)
Position: Chr6:41129260 G>A
dbSNP ID: rs104894001
Coding/Non-Coding: Coding
Mutation Type: Point, Nonsense
Codon Change: TGG to TGA
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 2

Findings

The rs104894001 variant introduces a premature stop codon in place of tryptophan at amino acid 44. This variant, in a homozygous state, was found in a Bolivian patient 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 (FTD) (Paloneva et al., 2002). The variant was not found in a control group of 100 Caucasian individuals.

Neuropathology

Unknown. Brain atrophy was reported in the 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 2018

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References

Paper Citations

  1. . 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. . 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. . 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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