Overview

Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity, Frontotemporal Dementia : Unclear Pathogenicity
Reference Assembly: GRCh37/hg19
Position: Chr6:41129100 C>T
dbSNP ID: rs147564421
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: CGG to TGG
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 2

Findings

In a Caucasian cohort, the R98W variant was found in one of 1091 Alzheimer’s patients and none of 1107 cognitively healthy controls (Guerreiro et al., 2013).  In another study, of Italian subjects, the variant was found in one of 194 Alzheimer’s patients, none of 352 FTD patients, and one of 484 controls (Borroni et al., 2014).  The variant was not found in a Japanese study that included approximately 2200 AD patients and 2500 controls (Miyashita et al., 2014).

Neuropathology

No data.

Biological Effect

The arginine-to-tryptophan substitution at amino acid 98 was predicted to be probably damaging by PolyPhen2 (Guerreiro et al., 2013).

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References

Paper Citations

1. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J, Alzheimer Genetic Analysis Group. TREM2 variants in Alzheimer's disease. N Engl J Med. 2013 Jan 10;368(2):117-27. Epub 2012 Nov 14 PubMed.
2. Borroni B, Ferrari F, Galimberti D, Nacmias B, Barone C, Bagnoli S, Fenoglio C, Piaceri I, Archetti S, Bonvicini C, Gennarelli M, Turla M, Scarpini E, Sorbi S, Padovani A. Heterozygous TREM2 mutations in frontotemporal dementia. Neurobiol Aging. 2014 Apr;35(4):934.e7-10. Epub 2013 Oct 16 PubMed.
3. Miyashita A, Wen Y, Kitamura N, Matsubara E, Kawarabayashi T, Shoji M, Tomita N, Furukawa K, Arai H, Asada T, Harigaya Y, Ikeda M, Amari M, Hanyu H, Higuchi S, Nishizawa M, Suga M, Kawase Y, Akatsu H, Imagawa M, Hamaguchi T, Yamada M, Morihara T, Takeda M, Takao T, Nakata K, Sasaki K, Watanabe K, Nakashima K, Urakami K, Ooya T, Takahashi M, Yuzuriha T, Serikawa K, Yoshimoto S, Nakagawa R, Saito Y, Hatsuta H, Murayama S, Kakita A, Takahashi H, Yamaguchi H, Akazawa K, Kanazawa I, Ihara Y, Ikeuchi T, Kuwano R. Lack of genetic association between TREM2 and late-onset Alzheimer's disease in a Japanese population. J Alzheimers Dis. 2014;41(4):1031-8. PubMed.

Further Reading

No Available Further Reading