Overview

Pathogenicity: Frontotemporal Dementia : Benign
Clinical Phenotype: Frontotemporal Dementia
Position: (GRCh38/hg38):Chr17:46010390 G>A
Position: (GRCh37/hg19):Chr17:44087756 G>A
dbSNP ID: rs63751395
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Silent
Codon Change: CCG to CCA
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 10

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 available. 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 3R to 4R tau isoforms (Miyamoto et al., 2001).

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References

Paper Citations

1. Miyamoto K, Kowalska A, Hasegawa M, Tabira T, Takahashi K, Araki W, Akiguchi I, Ikemoto A. 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 Citations

1. IVS10+11

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database