Mutations

MAPT A239T

Overview

Pathogenicity: Frontotemporal Dementia : Benign
Clinical Phenotype: Frontotemporal Dementia
Position: (GRCh38/hg38):Chr17:45996557 G>A
Position: (GRCh37/hg19):Chr17:44073923 G>A
dbSNP ID: rs63750096
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GCC to ACC
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 9

Findings

This variant was detected in a British individual with frontotemporal dementia who was affected by a rare tau-negative microvacuolar-type pathology. The variant was absent in more than 900 controls; however, lack of DNA from family members precluded segregation analysis (Pickering-Brown et al., 2002). A follow-up study showed that this individual also carried a deletion mutation in GRN (IVS10-16_Ex11+177del194 bp), which is associated with FTD pathogenicity. The MAPT variant therefore is thought to be a rare benign polymorphism present alongside the GRN deletion responsible for disease in this individual (Pickering-Brown et al., 2006).

Neuropathology

This varient was detected in an individual with a rare tau-negative microvacuolar-type neuropathology; however, the disease was attributed to a co-occuring GRN deletion mutation (Pickering-Brown et al., 2006).

Biological Effect

Unknown.

Last Updated: 18 Jul 2024

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References

Paper Citations

  1. Pickering-Brown SM, Richardson AM, Snowden JS, McDonagh AM, Burns A, Braude W, Baker M, Liu WK, Yen SH, Hardy J, Hutton M, Davies Y, Allsop D, Craufurd D, Neary D, Mann DM. Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene. Brain. 2002 Apr;125(Pt 4):732-51. PubMed.
  2. Pickering-Brown SM, Baker M, Gass J, Boeve BF, Loy CT, Brooks WS, Mackenzie IR, Martins RN, Kwok JB, Halliday GM, Kril J, Schofield PR, Mann DM, Hutton M. Mutations in progranulin explain atypical phenotypes with variants in MAPT. Brain. 2006 Nov;129(Pt 11):3124-6. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. Pickering-Brown SM, Richardson AM, Snowden JS, McDonagh AM, Burns A, Braude W, Baker M, Liu WK, Yen SH, Hardy J, Hutton M, Davies Y, Allsop D, Craufurd D, Neary D, Mann DM. Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene. Brain. 2002 Apr;125(Pt 4):732-51. PubMed.

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