Mutations

MAPT Q230R

Overview

Pathogenicity: Frontotemporal Dementia : Benign, Alzheimer's Disease : Unclear Pathogenicity
Clinical Phenotype: Alzheimer's Disease, None
Reference Assembly: GRCh37/hg19
Position: Chr17:44060859 A>G
dbSNP ID: rs63750072
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: CAA to CGA
Reference Isoform: Tau Isoform PNS Tau (758 aa)
Genomic Region: Exon 4a

Findings

This variant is likely a benign polymorphism in MAPT (reviewed in Rademakers et al., 2004). It is located in exon 4a, which is excluded from the six major tau isoforms expressed in the human brain. The position of this mutation, 230, corresponds to the amino acid position in the PNS-tau isoform, which is present in the peripheral nervous system (Goedert et al., 1992; Georgieff et al., 1993).

This variant was detected in a study of individuals of Spanish descent (Jin et al., 2012). It was detected in 18 of 176 cases with Alzheimer's disease and in 8 out of 139 controls. Among those with AD, one was autopsy-confirmed, two had familial early-onset AD, two had familial late onset AD, and 13 had sporadic early-onset AD. Age of onset ranged from 50.5 to 83.5 years.

Last Updated: 29 May 2013

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References

Paper Citations

  1. Rademakers R, Cruts M, van Broeckhoven C. The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum Mutat. 2004 Oct;24(4):277-95. PubMed.
  2. Goedert M, Spillantini MG, Crowther RA. 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.
  3. Georgieff IS, Liem RK, Couchie D, Mavilia C, Nunez J, Shelanski ML. Expression of high molecular weight tau in the central and peripheral nervous systems. J Cell Sci. 1993 Jul;105 ( Pt 3):729-37. PubMed.
  4. Jin SC, Pastor P, Cooper B, Cervantes S, Benitez BA, Razquin C, Goate A, Ibero-American Alzheimer Disease Genetics Group Researchers, Cruchaga C. Pooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early-onset and familial Alzheimer's disease Ibero-American cohort. Alzheimers Res Ther. 2012 Aug 20;4(4):34. PubMed.

External Citations

  1. PNS-tau

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. Rademakers R, Cruts M, van Broeckhoven C. The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum Mutat. 2004 Oct;24(4):277-95. PubMed.

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