Mutations

MAPT G389R (G>A)

Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic, Other Tauopathy : Pathogenic
Clinical Phenotype: Frontotemporal Dementia, Pick's disease
Genomic Mutation Name (MET1): g.137420G>A
Genomic Mutation Name (NT1): g.134598G>A
dbSNP ID: rs63750512
Coding/Non-Coding: Coding
Genomic Region: Exon 13
Mutation Type: Point, Missense
Codon Change: GGG to AGG

Findings

This mutation was first identified in one out of 30 cases of pathologically confirmed Pick's disease. At age 32 the patient began to show a decline in intellectual ability, along with forgetfulness, aggression, and a decline in personal hygiene. She deteriorated rapidly and died at age of 37. The proband's brain showed severe atrophy of the frontal lobe with severe neuronal loss and astrocytosis with marked tissue vacuolation in the frontal cortex. The hippocampus was relatively preserved, with mild neuronal loss in area CA1, but no neuritic plaques or neurofibrillary tangles (Pickering-Brown et al., 2000).

This mutation was also found in a young Australian patient with characteristics of FTDP-17 with symptom onset at age 20 and a disease duration of four years. Postmortem examination showed severe cortical atrophy, predominantly of frontal and temporal lobes, with relative sparing of the parietal and occipital lobes (Bermingham et al., 2008).

Biological Effect

Recombinant G389R tau showed a reduced ability to promote microtubule assembly and an increased susceptibility to calpain I digestion (Pickering-Brown et al., 2000).

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References

Paper Citations

  1. . Pick's disease is associated with mutations in the tau gene. Ann Neurol. 2000 Dec;48(6):859-67. PubMed.
  2. . Frontotemporal dementia and Parkinsonism linked to chromosome 17 in a young Australian patient with the G389R Tau mutation. Neuropathol Appl Neurobiol. 2008 Jun;34(3):366-70. Epub 2007 Dec 7 PubMed.

Further Reading

Papers

  1. . Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by progranulin and tau mutations. Neuroimage. 2010 Nov 15;53(3):1070-6. Epub 2010 Jan 4 PubMed.

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Pick's disease is associated with mutations in the tau gene. Ann Neurol. 2000 Dec;48(6):859-67. PubMed.

Other mutations at this position

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