Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Position: (GRCh38/hg38):Chr17:45996620 A>G
Position: (GRCh37/hg19):Chr17:44073986 A>G
dbSNP ID: rs63751249
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: ATC to GTC
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 9

Findings

I260V was the fourth mutation identified in the first microtubule-binding domain of tau (encoded by exon 9) to be associated with frontotemporal dementia. The previously reported mutations were K257T, L266V, and G272V.

Neuropathology

Unlike the previous mutations in exon 9, I260V is associated with deposition of four-repeat (4R) tau and has a pathological phenotype that lacks Pick body-like lesions (Grover et al., 2003). Neurofibrillary tangles also were not observed. Sarkosyl-insoluble tau extracted from affected brain tissue consisted almost exclusively of 4R isoforms.

Biological Effect

In vitro biochemical assays demonstrated that I260V causes a selective increase in 4R tau aggregation (Grover et al., 2003).

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References

Paper Citations

1. Grover A, England E, Baker M, Sahara N, Adamson J, Granger B, Houlden H, Passant U, Yen SH, DeTure M, Hutton M. A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy. Exp Neurol. 2003 Nov;184(1):131-40. PubMed.

Other Citations

1. K257T

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database