Overview

Pathogenicity: Other Tauopathy : Pathogenic, Frontotemporal Dementia : Benign
Clinical Phenotype: Progressive Supranuclear Palsy
Position: (GRCh38/hg38):Chr17:46010395 G>T
Position: (GRCh37/hg19):Chr17:44087761 G>T
dbSNP ID: rs63751391
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 10

Findings

This mutation is associated with autosomal-dominant progressive supranuclear palsy. It was reported in a family with three affected family members over two generations. Starting at age 37, the proband developed akinetic-rigid syndrome, gait disturbance, and frequent falls, among other symptoms. She died at age 45. The two other affected family members had a similar age of onset (41 and late 30s) and age at death (45 and 41) (Ros et al., 2005).

Neuropathology

Neuropathological analysis of the proband's brain showed atrophy of the mesencephalon, pons, striatum, and subthalamic nuclei. The substantia nigra was depigmented and showed neuronal loss, mild spongiosis, and gliosis. Ventricles were enlarged and there was mild atrophy of the frontotemporal cortex. Tau accumulations were seen in neurons and glia, including neurofibrillary tangles. The brain was noted to have an increase in 4-repeat (4R) isoforms of tau (Ros et al., 2005).

Biological Effect

Unknown.

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References

Paper Citations

1. Ros R, Thobois S, Streichenberger N, Kopp N, Sánchez MP, Pérez M, Hoenicka J, Avila J, Honnorat J, de Yébenes JG. A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy. Arch Neurol. 2005 Sep;62(9):1444-50. PubMed.

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database