Mutations

MAPT P301P

Overview

Pathogenicity: Frontotemporal Dementia : Not Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Genomic Mutation Name (MET1): g.123791G>A
Genomic Mutation Name (NT1): g.120970G>A
dbSNP ID: rs63751395
Coding/Non-Coding: Coding
Genomic Region: Exon 10
Mutation Type: Point, Silent
Codon Change: CCG to CCA

Findings

This mutation was reported in a 51 year-old Japanese man with frontotemporal dementia and parkinsonism. The clinical presentation was unusual in that the proband had early onset intellectual difficulties (within the first decade of life) as well as difficulties walking (he didn't walk until age 10). He died at age 54. His mother, grandfather, and at least two siblings had similar illnesses, but DNA was not unavailable. The mutation was not present in his unaffected sister. The proband also had an intronic mutation in MAPT, IVS10+11, and this was determined to be the likely pathogenic allele because the P301P mutation did not alter the ratio of 3-repeat (3R) to 4-repeat (4R) tau, but the IVS10+11 variant did (Miyamoto et al., 2001).

Neuropathology

The proband's brain was characterized by severe neuronal loss in the frontal and temporal cortices, globus pallidus, substantia nigra, red nucleus and dentate nucleus. Tau-positive fibrillar structures were observed in neurons and glia in these regions (Miyamoto et al., 2001).

Biological Effect

This mutation was not associated with a change in the ratio of 3-repeat to 4-repeat tau isoforms (Miyamoto et al., 2001).

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References

Mutations Citations

  1. MAPT IVS10+11 T>C

Paper Citations

  1. . Familial frontotemporal dementia and parkinsonism with a novel mutation at an intron 10+11-splice site in the tau gene. Ann Neurol. 2001 Jul;50(1):117-20. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Familial frontotemporal dementia and parkinsonism with a novel mutation at an intron 10+11-splice site in the tau gene. Ann Neurol. 2001 Jul;50(1):117-20. PubMed.

Other mutations at this position

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