Mutations

MAPT G389R (G>C)

Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Genomic Mutation Name (MET1): g.137420G>C
Genomic Mutation Name (NT1): g.134598G>C
dbSNP ID: rs63750512
Coding/Non-Coding: Coding
Genomic Region: Exon 13
Mutation Type: Point, Missense
Codon Change: GGG to CGG

Findings

This mutation was first identified in a 38-year-old patient presenting with progressive aphasia and memory disturbance, followed by apathy, indifference, hyperphagia, rigidity, pyramidal signs, and profound dementia, with death at age 43. A paternal uncle had died at age 43 with similar symptoms. The proband's brain showed numerous tau-positive Pick body-like inclusions in the neocortex and numerous tau-positive filamentous inclusions in axons in the frontal, temporal, and parietal lobes, and severe cerebral atrophy (Murrell et al., 1999; Ghetti et al., 2000).

This mutation was also identified in an apparently sporadic case of corticobasal syndrome (CBS). The patient was a 41-year-old man with progressive asymmetric signs of cortical and basal ganglia involvement consistent with CBS. MRI showed asymmetric cortical atrophy. The mutation was present in the proband's unaffected elderly father, suggesting possible incomplete penetrance (Rossi et al., 2008). 

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References

Paper Citations

  1. . Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits. J Neuropathol Exp Neurol. 1999 Dec;58(12):1207-26. PubMed.
  2. . Progress in hereditary tauopathies: a mutation in the Tau gene (G389R) causes a Pick disease-like syndrome. Ann N Y Acad Sci. 2000;920:52-62. PubMed.
  3. . The G389R mutation in the MAPT gene presenting as sporadic corticobasal syndrome. Mov Disord. 2008 Apr 30;23(6):892-5. PubMed.

Further Reading

Papers

  1. . Slow wave and rem sleep mechanisms are differently altered in hereditary pick disease associated with the TAU G389R mutation. Arch Ital Biol. 2005 Feb;143(1):65-79. PubMed.
  2. . Reduced binding of protein phosphatase 2A to tau protein with frontotemporal dementia and parkinsonism linked to chromosome 17 mutations. J Neurochem. 2000 Nov;75(5):2155-62. PubMed.

Learn More

Primary Papers

  1. . Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits. J Neuropathol Exp Neurol. 1999 Dec;58(12):1207-26. PubMed.
  2. . Progress in hereditary tauopathies: a mutation in the Tau gene (G389R) causes a Pick disease-like syndrome. Ann N Y Acad Sci. 2000;920:52-62. PubMed.
  3. . The G389R mutation in the MAPT gene presenting as sporadic corticobasal syndrome. Mov Disord. 2008 Apr 30;23(6):892-5. PubMed.

Other mutations at this position

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