Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia, Tauopathy consistent with Pick's Disease
Reference Assembly: GRCh37/hg19
Position: Chr17:44096092 A>T
dbSNP ID: rs63751264
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: AAA to ATA
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 12

Findings

This mutation was identified in a 50-year-old woman of German origin presenting first with depression and dramatic personality changes, followed by loss of cognitive function. The patient continued to deteriorate and died at the age of 61. Family history was unavailable, and therefore it was not possible to assess whether the mutation segregated with disease. The mutation was not found in 100 cognitively healthy controls (Neumann et al., 2001).

Neuropathology

Postmortem examination showed brain atrophy, which was most pronounced in the temporal lobes. Numerous tau-positive Pick bodies and Pick cells indistinguishable from those of sporadic Pick's disease were observed in the neocortex, hippocampus, and subcortical brain regions (Neumann et al., 2001).

Biological Effect

Recombinant tau proteins with the K369I mutation showed reduced ability to promote microtubule assembly (Neumann et al., 2001).

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References

Paper Citations

1. Neumann M, Schulz-Schaeffer W, Crowther RA, Smith MJ, Spillantini MG, Goedert M, Kretzschmar HA. Pick's disease associated with the novel Tau gene mutation K369I. Ann Neurol. 2001 Oct;50(4):503-13. PubMed.

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database