Overview

Pathogenicity: Frontotemporal Dementia : Not Pathogenic, Other Tauopathy : Unclear Pathogenicity
Clinical Phenotype: Argyrophilic Grain Disease
Reference Assembly: GRCh37 (105)
Position: Chr17:44087767 G>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Genomic Region: Exon 10
Mutation Type: Point, Missense
Codon Change: AGT to ATT

Findings

This mutation was identified in a Hungarian individual who at the age of 39 developed behavior and personality changes. He rapidly developed progressive speech and movement disorders with cognitive impairment, depression, and anxiety. He died at age 41 with symmetric parkinsonism, vertical gaze palsy, bulbar symptoms, and severe dementia. The patient's clinical presentation and neuropathology are consistent with the sporadic tauopathy argyrophilic grain disease. Pathogenicity could not be determined, but the mutation was absent in 95 Hungarian controls (Kovacs et al., 2008).

Neuropathology

Neuropathological analysis showed extensive neuronal loss in the medial temporal cortex, hippocampus, and amygdala. Classical neurofibrillary tangles, Pick bodies, and neuritic plaques were not observed. There was evidence of diffuse cytoplasmic tau staining in neurons, coiled bodies in oligodendrocytes, and argyrophilic grains. The tau-positive structures were composed only of 4-repeat (4R) tau isoforms (Kovacs et al., 2008).

Biological Effect

This mutation affects exon 10 splicing, causing an overproduction of 4-repeat (4R) tau isoforms (Kovacs et al., 2008).

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References

Paper Citations

1. Kovacs GG, Pittman A, Revesz T, Luk C, Lees A, Kiss E, Tariska P, Laszlo L, Molnár K, Molnar MJ, Tolnay M, de Silva R. MAPT S305I mutation: implications for argyrophilic grain disease. Acta Neuropathol. 2008 Jul;116(1):103-18. Epub 2007 Dec 8 PubMed.

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database