Overview

Pathogenicity: Frontotemporal Dementia : Incomplete Penetrance
Clinical Phenotype: Frontotemporal Dementia, None
Reference Assembly: GRCh37/hg19
Position: Chr17:44091637 T>G
dbSNP ID: rs63749855
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: CTG to CGG
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 11

Findings

This mutation was originally described in two Dutch families with frontotemporal dementia. The age at onset was variable within each family, ranging from 25 to 64 years, and at least one mutation carrier reached the age of 82 with no signs of dementia, suggesting possible incomplete penetrance (van Herpen et al., 2003).

Neuropathology

Postmortem examination showed that affected individuals had extensive tau pathology in neurons (Pick-like inclusions) and astrocytes, particularly in the frontotemporal cortex and hippocampus. Tau extracted from the cerebral cortex was present in straight and twisted tau filaments (van Herpen et al., 2003).

Biological Effect

Recombinant L315R tau protein has a compromised ability to promote microtubule assembly (van Herpen et al., 2003).

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References

Paper Citations

1. van Herpen E, Rosso SM, Serverijnen LA, Yoshida H, Breedveld G, van de Graaf R, Kamphorst W, Ravid R, Willemsen R, Dooijes D, Majoor-Krakauer D, Kros JM, Crowther RA, Goedert M, Heutink P, van Swieten JC. Variable phenotypic expression and extensive tau pathology in two families with the novel tau mutation L315R. Ann Neurol. 2003 Nov;54(5):573-81. PubMed.

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database