Overview

Pathogenicity: Nasu-Hakola Disease : Pathogenic
Clinical Phenotype: Nasu-Hakola Disease
Position: (GRCh38/hg38):Chr6:41163043 G>T
Position: (GRCh37/hg19):Chr6:41130781 G>T
dbSNP ID: rs386834143
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Nonsense
Codon Change: GAG to TAG
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 1

Findings

The rs386834143 variant introduces a premature stop codon in place of glutamate at amino acid 14. This variant, in a homozygous state, was found in a German patient affected by Nasu-Hakola disease (NHD; also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy) (Paloneva et al., 2003), a rare autosomal-recessive disease characterized by bone cysts and early onset frontotemporal dementia (FTD) (Paloneva et al., 2002).

Neuropathology

Unknown.

Biological Effect

TREM2 transcripts were not detected in peripheral blood mononuclear cells isolated from the patient homozygous for the E14X variant, consistent with the presence of the premature stop codon (Paloneva et al., 2003).

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References

Paper Citations

1. Paloneva J, Mandelin J, Kiialainen A, Bohling T, Prudlo J, Hakola P, Haltia M, Konttinen YT, Peltonen L. DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. J Exp Med. 2003 Aug 18;198(4):669-75. 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