Mutations

MAPT D285N

Overview

Pathogenicity: Frontotemporal Dementia : Benign, Other Tauopathy : Incomplete Penetrance
Clinical Phenotype: Progressive Supranuclear Palsy, None
Position: (GRCh38/hg38):Chr17:45983657 G>A
Position: (GRCh37/hg19):Chr17:44061023 G>A
dbSNP ID: rs62063786
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GAC to AAC
Reference Isoform: Tau Isoform PNS Tau (758 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 the six major tau isoforms expressed in the human brain, but it is present in PNS-tau (P10636-1) and Tau-G (P10636-9), which are 758 and 776 amino acids long, respectively. Therefore, the position of this variant is in reference to these isoforms, rather than to isoform Tau-F (P10636-8).

Neuropathology

Not applicable.

Biological Effect

Unknown.

Last Updated: 31 Dec 2012

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References

Paper Citations

  1. Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WC, Raskind M, Schellenberg GD. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998 Jun;43(6):815-25. PubMed.
  2. Higgins JJ, Adler RL, Loveless JM. Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology. 1999 Oct 22;53(7):1421-4. PubMed.

External Citations

  1. P10636-1
  2. P10636-9
  3. P10636-8

Further Reading

Papers

  1. Higgins JJ, Golbe LI, De Biase A, Jankovic J, Factor SA, Adler RL. An extended 5'-tau susceptibility haplotype in progressive supranuclear palsy. Neurology. 2000 Nov 14;55(9):1364-7. PubMed.
  2. Ingelson M, Fabre SF, Lilius L, Andersen C, Viitanen M, Almkvist O, Wahlund LO, Lannfelt L. Increased risk for frontotemporal dementia through interaction between tau polymorphisms and apolipoprotein E epsilon4. Neuroreport. 2001 Apr 17;12(5):905-9. PubMed.
  3. Stanford PM, Brooks WS, Teber ET, Hallupp M, McLean C, Halliday GM, Martins RN, Kwok JB, Schofield PR. 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. Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WC, Raskind M, Schellenberg GD. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998 Jun;43(6):815-25. PubMed.
  2. Higgins JJ, Adler RL, Loveless JM. Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology. 1999 Oct 22;53(7):1421-4. PubMed.

Other mutations at this position

View Table

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