Overview

Pathogenicity: Frontotemporal Dementia : Unclear Pathogenicity
Clinical Phenotype: None
Position: (GRCh38/hg38):Chr17:45974420 G>A
Position: (GRCh37/hg19):Chr17:44051786 G>A
dbSNP ID: rs63751135
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GGC to AGC
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 3

Findings

This mutation was identified in a woman diagnosed with frontotemporal dementia with onset at age 71. She presented with decreased concentration and activity, distractibility, perseveration, and personality changes. She later developed frontal release signs and seizures, and became mute and unable to walk without assistance. The proband had a positive family history of neurodegenerative disease, including a mother with unspecified dementia and two siblings with clinical features consistent with Alzheimer's disease. The mutation was not present in either sibling and the mother's DNA was unavailable. The mutation was also absent in 100 control chromosomes, but pathogenicity could not be determined (Stanford et al., 2004).

Neuropathology

Unknown. A PET scan showed frontal hypometabolism (Stanford et al., 2004).

Biological Effect

Exon-trapping experiments indicate that the G86S mutation does not alter the normal splicing of exons 2 or 3. The amino acid substitution results in the creation of phosphorylation and O-glycosylation sites, as predicted (Stanford et al., 2004).

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References

Paper Citations

1. Stanford PM, Brooks WS, Teber ET, Hallupp M, McLean C, Halliday GM, Martins RN, Kwok JB, Schofield PR. Frequency of tau mutations in familial and sporadic frontotemporal dementia and other tauopathies. J Neurol. 2004 Sep;251(9):1098-104. PubMed.

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database