Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Behavioral variant FTD
Reference Assembly: GRCh37/hg19
Position: Chr6:41126693 G>A
dbSNP ID: NA
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: TGG to TGA
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 4

Findings

The W198X variant introduces a premature stop codon in place of tryptophan 198. This variant was found to segregate with disease in a Colombian family with autosomal recessive behavioral variant FTD (Giraldo et al., 2013). The clinical course has been described for three homozygous carriers of the W198X mutation. Changes in social behavior, beginning between 45 and 60 years of age, were followed by apathy, disinhibition and impulsivity, obsessive and perseverative behavior, and cognitive deficits. Two of the patients also experienced complex partial seizures. 

Neuropathology

Neuropathological characterization of NHD patients carrying this variant is currently lacking. However, frontal lobe atrophy was observed in the one patient who had undergone MRI (Giraldo et al., 2013).

Biological Effect

This variant is predicted to result in premature truncation of the protein.

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References

Paper Citations

1. Giraldo M, Lopera F, Siniard AL, Corneveaux JJ, Schrauwen I, Carvajal J, Muñoz C, Ramirez-Restrepo M, Gaiteri C, Myers AJ, Caselli RJ, Kosik KS, Reiman EM, Huentelman MJ. Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease. Neurobiol Aging. 2013 Aug;34(8):2077.e11-8. Epub 2013 Apr 9 PubMed.

Further Reading

No Available Further Reading