Mutations
MAPT L315R
Quick Links
Overview
Pathogenicity: Frontotemporal Dementia : Incomplete Penetrance
Clinical
Phenotype: Frontotemporal Dementia, None
Position: (GRCh38/hg38):Chr17:46014271 T>G
Position: (GRCh37/hg19):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).
Last Updated: 18 Jul 2024
References
Paper Citations
- 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
Papers
- Rosso SM, Donker Kaat L, Baks T, Joosse M, de Koning I, Pijnenburg Y, de Jong D, Dooijes D, Kamphorst W, Ravid R, Niermeijer MF, Verheij F, Kremer HP, Scheltens P, van Duijn CM, Heutink P, van Swieten JC. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain. 2003 Sep;126(Pt 9):2016-22. Epub 2003 Jul 22 PubMed.
Learn More
Protein Diagram
Primary Papers
- 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.
Other mutations at this position
Alzpedia
Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.
Comments
No Available Comments
Make a Comment
To make a comment you must login or register.