Mutations

MAPT S320F

Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia, Tauopathy consistent with Pick's Disease
Position: (GRCh38/hg38):Chr17:46014286 C>T
Position: (GRCh37/hg19):Chr17:44091652 C>T
dbSNP ID: rs63750635
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: TCC to TTC
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 11

Findings

The S320F mutation was the first mutation identified in exon 11 of MAPT. The proband developed symptoms at age 38, primarily mild memory problems and spatial disorientation. He was originally diagnosed with Alzheimer's disease. He died at age 53 and postmortem examination revealed neuropathology resembling Pick’s disease. The brain contained tau-positive inclusions characterized by straight and twisted filaments, similar to those described in sporadic Pick's disease. Soluble tau extracted from the brain  consisted of multiple tau isoforms, including the six major isoforms expressed in the CNS (Rosso et al., 2002).

Neuropathology

Autopsy showed neuropathology resembling Pick’s disease including focal bilateral atrophy of the anterior temporal lobes with only very mild frontal atrophy. Severe neuronal loss and gliosis were present in the temporal cortex, cingulate gyrus, entorhinal cortex, and hippocampus. The substantia nigra was not affected (Rosso et al., 2002).

Biological Effect

The S320F mutation causes a marked reduction in the ability of tau to promote microtubule assembly. It also removes a potential phosphorylation site in tau (Rosso et al., 2002).

Last Updated: 18 Jul 2024

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References

Paper Citations

  1. Rosso SM, van Herpen E, Deelen W, Kamphorst W, Severijnen LA, Willemsen R, Ravid R, Niermeijer MF, Dooijes D, Smith MJ, Goedert M, Heutink P, van Swieten JC. A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick's disease. Ann Neurol. 2002 Mar;51(3):373-6. PubMed.

Further Reading

Papers

  1. Rosso SM, Donker Kaat L, Baks T, Joosse M, de Koning I, Pijnenburg Y, de Jong D, Dooijes D, Kamphorst W, Ravid R, Niermeijer MF, Verheij F, Kremer HP, Scheltens P, van Duijn CM, Heutink P, van Swieten JC. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain. 2003 Sep;126(Pt 9):2016-22. Epub 2003 Jul 22 PubMed.
  2. Rohrer JD, Guerreiro R, Vandrovcova J, Uphill J, Reiman D, Beck J, Isaacs AM, Authier A, Ferrari R, Fox NC, Mackenzie IR, Warren JD, de Silva R, Holton J, Revesz T, Hardy J, Mead S, Rossor MN. The heritability and genetics of frontotemporal lobar degeneration. Neurology. 2009 Nov 3;73(18):1451-6. PubMed.
  3. Rohrer JD, Ridgway GR, Modat M, Ourselin S, Mead S, Fox NC, Rossor MN, Warren JD. Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by progranulin and tau mutations. Neuroimage. 2010 Nov 15;53(3):1070-6. Epub 2010 Jan 4 PubMed.

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. Rosso SM, van Herpen E, Deelen W, Kamphorst W, Severijnen LA, Willemsen R, Ravid R, Niermeijer MF, Dooijes D, Smith MJ, Goedert M, Heutink P, van Swieten JC. A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick's disease. Ann Neurol. 2002 Mar;51(3):373-6. PubMed.

Other mutations at this position

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