Mutations

MAPT D285N

Overview

Pathogenicity: Frontotemporal Dementia : Not Pathogenic, Other Tauopathy : Incomplete Penetrance
Clinical Phenotype: Progressive Supranuclear Palsy, None
Reference Assembly: GRCh37 (105)
Position: Chr17:44061023 G>A
dbSNP ID: rs62063786
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GAC to AAC
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 4a

Findings

This variant was first described in subjects with frontotemporal dementia with parkinsonism-17 and also in healthy controls (Poorkaj et al., 1998).

This variant has been associated with an increased risk of developing progressive supranuclear palsy (PSP) (Higgins et al., 1999).

Exon 4a is excluded from most tau isoforms, but is present in a large isoform known as PNS-tau that is expressed primarily in the peripheral nervous system (Goedert et al., 1992; Georgieff et al., 1993). The position of this variant (285) is numbered according to amino acid position in PNS-tau rather than in isoform 441 (TauF).

Neuropathology

Not applicable.

Biological Effect

Unknown.

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References

Paper Citations

  1. . Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998 Jun;43(6):815-25. PubMed.
  2. . Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology. 1999 Oct 22;53(7):1421-4. PubMed.
  3. . Cloning of a big tau microtubule-associated protein characteristic of the peripheral nervous system. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1983-7. PubMed.
  4. . Expression of high molecular weight tau in the central and peripheral nervous systems. J Cell Sci. 1993 Jul;105 ( Pt 3):729-37. PubMed.

External Citations

  1. PNS-tau

Further Reading

Papers

  1. . An extended 5'-tau susceptibility haplotype in progressive supranuclear palsy. Neurology. 2000 Nov 14;55(9):1364-7. PubMed.
  2. . Increased risk for frontotemporal dementia through interaction between tau polymorphisms and apolipoprotein E epsilon4. Neuroreport. 2001 Apr 17;12(5):905-9. PubMed.
  3. . Frequency of tau mutations in familial and sporadic frontotemporal dementia and other tauopathies. J Neurol. 2004 Sep;251(9):1098-104. PubMed.

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998 Jun;43(6):815-25. PubMed.
  2. . Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology. 1999 Oct 22;53(7):1421-4. PubMed.

Other mutations at this position

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