Mutations

MAPT IVS10+11 T>C

Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Position: (GRCh38/hg38):Chr17:46010413 T>C
Position: (GRCh37/hg19):Chr17:44087779 T>C
dbSNP ID: rs63751394
Coding/Non-Coding: Non-Coding
DNA Change: Substitution
Expected RNA Consequence: Splicing Alteration
Expected Protein Consequence: Isoform Shift
Codon Change: T to C
Genomic Region: Intron 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 a silent mutation in MAPT (P301P), but unlike the IVS10+11 mutation, the P301P mutation did not alter the ratio of 3-repeat (3R) to 4-repeat (4R) tau, leading the authors to conclude that the IVS10+11 mutation was likely to be the pathogenic allele (Miyamoto et al., 2001; Kowalska et al., 2002).

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 is associated with an increase in 4R tau relative to 3R tau (Miyamoto et al., 2001).

Last Updated: 18 Jul 2024

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References

Mutations Citations

  1. MAPT P301P

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.
  2. Kowalska A, Hasegawa M, Miyamoto K, Akiguchi I, Ikemoto A, Takahashi K, Araki W, Tabira T. A novel mutation at position +11 in the intron following exon 10 of the tau gene in FTDP-17. J Appl Genet. 2002;43(4):535-43. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. Kowalska A, Hasegawa M, Miyamoto K, Akiguchi I, Ikemoto A, Takahashi K, Araki W, Tabira T. A novel mutation at position +11 in the intron following exon 10 of the tau gene in FTDP-17. J Appl Genet. 2002;43(4):535-43. PubMed.
  2. 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.

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