Mutations

MAPT V363I

Overview

Pathogenicity: Frontotemporal Dementia : Incomplete Penetrance
Clinical Phenotype: Frontotemporal Dementia
Position: (GRCh38/hg38):Chr17:46018707 G>A
Position: (GRCh37/hg19):Chr17:44096073 G>A
dbSNP ID: rs63750869
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GTC to ATC
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 12

Findings

The V363I mutation was first identified in a woman presenting with progressive nonfluent aphasia at the age of 69. By age 75 her language difficulties had progressed such that she was nearly mute, and she had also developed gait and swallowing disturbances. Her father had reportedly exhibited late-onset aphasia and apraxia. A mutation-carrying sibling showed no abnormalities at age 70, consistent with reduced penetrance. The mutation was absent in 194 control individuals from a similar genetic background (Munoz et al., 2007).

In an unrelated family, this mutation was identified in a 56-year-old woman who presented with disturbed behavior and cognitive deterioration. She was diagnosed with frontotemporal dementia and died at the age of 61. In this study the mutation was absent in 100 cognitively healthy controls, but present in several of the proband's unaffected family members. Whether the mutation is incompletely penetrant or a rare polymorphism could not be determined (Anfossi et al., 2011).

Neuropathology

Unknown. MRI showed massive brain atrophy in one individual with FTD (Anfossi et al., 2011).

Biological Effect

Unknown.

Last Updated: 18 Jul 2024

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References

Paper Citations

  1. Anfossi M, Bernardi L, Gallo M, Geracitano S, Colao R, Puccio G, Curcio SA, Frangipane F, Mirabelli M, Tomaino C, Smirne N, Maletta R, Bruni AC. MAPT V363I variation in a sporadic case of frontotemporal dementia: variable penetrant mutation or rare polymorphism?. Alzheimer Dis Assoc Disord. 2011 Jan-Mar;25(1):96-9. PubMed.
  2. Munoz DG, Ros R, Fatas M, Bermejo F, de Yebenes JG. Progressive nonfluent aphasia associated with a new mutation V363I in tau gene. Am J Alzheimers Dis Other Demen. 2007 Aug-Sep;22(4):294-9. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. Munoz DG, Ros R, Fatas M, Bermejo F, de Yebenes JG. Progressive nonfluent aphasia associated with a new mutation V363I in tau gene. Am J Alzheimers Dis Other Demen. 2007 Aug-Sep;22(4):294-9. PubMed.
  2. Anfossi M, Bernardi L, Gallo M, Geracitano S, Colao R, Puccio G, Curcio SA, Frangipane F, Mirabelli M, Tomaino C, Smirne N, Maletta R, Bruni AC. MAPT V363I variation in a sporadic case of frontotemporal dementia: variable penetrant mutation or rare polymorphism?. Alzheimer Dis Assoc Disord. 2011 Jan-Mar;25(1):96-9. PubMed.

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