Interpretive Handbook

Test 87925 :
MAPT Gene, Sequence Analysis, Known Mutation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Frontotemporal dementia (FTLD) is a familial adult-onset, presenile dementia that affects the frontal and temporal cerebral cortices. Clinical presentation is variable and includes changes in behavior, difficulties with language, rigidity, palsy, and saccadic (rapid) eye movement. Symptoms generally begin between 40 and 60 years of age, with mean age of onset at approximately 45 years, and typically last between 5 and 10 years, progressing into severe dementia and mutism. The presentation of frontotemporal dementia may be confused with other dementias, including Alzheimer disease. It is important to distinguish between these different dementias because disease progression and patient management are different for the various dementias.


Based on the immunohistochemical staining, there are 2 main subtypes of FTLD: tau-positive FTLD and tau-negative FTLD with ubiquitin-positive inclusions (FTLD-U). Mutations in the MAPT gene have been identified in patients with tau-positive FTLD; mutations in the progranulin gene (GRN) have been identified in patients with FTLD-U. Both MAPT and GRN are located on chromosome 17q21.


The MAPT gene encodes the microtubule-associated tau protein. A number of mutations have been identified in the MAPT gene that result in aggregation of the tau protein. Although there is variable expression of disease presentation and severity within and between families, the hallmark neurologic lesion constitutes tau-positive protein inclusion bodies. Most clinically significant mutations are found in exons 9 through 13. Several intronic mutations, associated with alternative splicing of the mRNA, contribute to the variability of expression of the disease traits. Mutations in the MAPT gene have also been identified in cases of progressive supranuclear palsy, corticobasal degeneration, and dementia with epilepsy.

Useful For Suggests clinical disorders or settings where the test may be helpful

Screening of at-risk individuals when a mutation in the MAPT gene has been identified in an affected family member

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order MAPTM / MAPT Gene, Sequence Analysis, 7 Exon Screening Panel.


Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with frontotemporal dementia. This test can only be used for known mutations occurring in exons 1, 7, 9, 10, 11, 12, and 13 of the MAPT gene.


We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.


Predictive testing of an asymptomatic child is not recommended.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

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):277-295

2. Houlden H, Baker M, Adamson J, et al: Frequency of tau mutations in three series of non-Alzheimer’s degenerative dementia. Ann Neurol 1999 Aug;46(2):243-248

3. Goedert M: Tau protein and neurodegeneration. Semin Cell Dev Biol 2004 Feb;15(1):45-49

4. Dumanchin C, Camuzat A, Campion D, et al: Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotemporal dementia and parkinsonism. Hum Mol Genet 1998 Oct;7(11):1825-1829