Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Position: (GRCh38/hg38):Chr17:46018624 G>T
Position: (GRCh37/hg19):Chr17:44095990 G>T
dbSNP ID: rs63750905
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GGC to GTC
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 12

Findings

This mutation was identified in a German family with early onset frontotemporal dementia. At the age of 25, the proband presented with personality changes (lack of interest, unsocial behavior, and personal neglect) and was initially diagnosed with schizophrenia. Later the proband developed cognitive impairment with specific deficits in attention and executive functions. This mutation is likely to be pathogenic because it segregated with the clinical phenotype in a family with seven affected individuals and was not found in 100 unaffected individuals. The mean age at onset in this family was 25.4 years (Neumann et al., 2005). 

Neuropathology

Postmortem analysis is unavailable.

Biological Effect

The G335V mutation results in a dramatically reduced ability of tau to promote microtubule assembly and leads to an increased heparin-induced assembly of recombinant tau into filaments (Neumann et al., 2005).

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References

Paper Citations

1. Neumann M, Diekmann S, Bertsch U, Vanmassenhove B, Bogerts B, Kretzschmar HA. Novel G335V mutation in the tau gene associated with early onset familial frontotemporal dementia. Neurogenetics. 2005 May;6(2):91-5. Epub 2005 Mar 12 PubMed.

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database