Mutations

MAPT P301S

Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Genomic Mutation Name (MET1):
Genomic Mutation Name (NT1):
dbSNP ID: rs63751438
Coding/Non-Coding: Coding
Genomic Region: Exon 10
Mutation Type: Point, Missense
Codon Change: CCG to TCG
Research Models: 3

Findings

This mutation is associated with a variable clinical presentation. In one family, early onset frontotemporal dementia and parkinsonism was observed in combination with epileptic seizures (Sperfeld et al., 1999). In a three-generation Jewish-Algerian family, the P301S mutation was associated with personality changes in the late 30s followed by progressive cognitive and motor deterioration within one to two years, eventually leading to a state of akinetic mutism or death three to five years after symptom onset (Lossos et al., 2003). In another family, one individual presented with frontotemporal dementia, whereas his son was diagnosed with corticobasal degeneration. Disease onset was early in both, in the third decade of life, and progressed rapidly (Bugiani et al., 1999).

Neuropathology

Extensive filamentous hyperphosphorylated tau protein in neurons and glia (Bugiani et al., 1999; Sperfeld et al., 1999).

Biological Effect

Recombinant tau protein with the P301S mutation showed a greatly impaired ability to promote microtubule assembly (Bugiani et al., 1999).

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References

Paper Citations

  1. . FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation. Ann Neurol. 1999 Nov;46(5):708-15. PubMed.
  2. . Frontotemporal dementia and parkinsonism with the P301S tau gene mutation in a Jewish family. J Neurol. 2003 Jun;250(6):733-40. PubMed.
  3. . Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. J Neuropathol Exp Neurol. 1999 Jun;58(6):667-77. PubMed.

Further Reading

Papers

  1. . FTDP-17: phenotypical heterogeneity within P301S. Ann Neurol. 2000 Jul;48(1):126. PubMed.
  2. . The genetic and pathological classification of familial frontotemporal dementia. Arch Neurol. 2001 Nov;58(11):1813-6. PubMed.
  3. . A Japanese patient with frontotemporal dementia and parkinsonism by a tau P301S mutation. Neurology. 2000 Oct 24;55(8):1224-7. PubMed.
  4. . Dorsal root ganglion neurons carrying a P301S Tau mutation: a valid in vitro model for screening drugs against tauopathies?. J Neurosci. 2014 Apr 2;34(14):4757-9. PubMed.
  5. . Characteristics of frontotemporal dementia patients with a Progranulin mutation. Ann Neurol. 2006 Sep;60(3):374-80. PubMed.

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. J Neuropathol Exp Neurol. 1999 Jun;58(6):667-77. PubMed.
  2. . FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation. Ann Neurol. 1999 Nov;46(5):708-15. PubMed.
  3. . Frontotemporal dementia and parkinsonism with the P301S tau gene mutation in a Jewish family. J Neurol. 2003 Jun;250(6):733-40. PubMed.

Other mutations at this position

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