Interpretive Handbook

Test 87924 :
MAPT Gene, Sequence Analysis, 7 Exon Screening Panel

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

Frontotemporal dementia 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 to 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 progression and patient management are different for the various dementias.


Based on the immunohistochemical staining, there are 2 main subtypes of frontotemporal lobular degeneration (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

Aiding in the diagnosis of frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and dementia with epilepsy


Distinguishing the diagnosis of frontotemporal dementia from other dementias, including Alzheimer dementia


Identifying individuals who are at risk of frontotemporal dementia

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

Some individuals who are carriers or have a diagnosis of frontotemporal dementia may have a mutation that is not identified by this method (eg, mutations in other exons, promoter mutations). Mutations in other genes have also been implicated in frontotemporal dementia. Abnormalities in other genes are not detected by this assay. The absence of a mutation(s), therefore, does not eliminate the possibility of positive carrier status or the diagnosis of frontotemporal dementia. For carrier testing, it is important to first document the presence of a MAPT gene mutation in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


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.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

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 tau pathies. 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 a familial frontotemporal dementia and parkinsonism. Hum Mol Genet 1998 Oct;7(11):1825-1829