Overview

Pathogenicity: Other Tauopathy : Pathogenic
Clinical Phenotype: Progressive Supranuclear Palsy
Reference Assembly: GRCh37/hg19
Position: Chr17:44039717 G>T
dbSNP ID: rs63750959
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: CGC to CTC
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 1

Findings

This mutation was identified in a screen of MAPT in people with progressive supranuclear palsy. The R5L mutation was identified in one out of 96 PSP patients and in none of the 96 controls. The presenting clinical features of the patient included falls, dysarthria (difficulty pronouncing words), and micrographia (abnormally small, cramped handwriting), with onset at age 62 (Poorkaj et al., 2002).

Neuropathology

Aggregated insoluble tau in subcortical regions was predominantly 4-repeat (4R) tau with 0 or 1 amino terminal inserts (i.e. 0N4R or 1N4R). Insoluble tau in cortical regions also contained 1N3R tau (Poorkaj et al., 2002).

Biological Effect

This missense mutation alters the tau protein's ability to promote microtubule assembly. It does not appear to affect the ratio of tau isoforms synthesized (Poorkaj et al., 2002).

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References

Paper Citations

1. Poorkaj P, Muma NA, Zhukareva V, Cochran EJ, Shannon KM, Hurtig H, Koller WC, Bird TD, Trojanowski JQ, Lee VM, Schellenberg GD. An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. Ann Neurol. 2002 Oct;52(4):511-6. PubMed.

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database