Interpretive Handbook

Test 89187 :
Progranulin Gene (GRN), Known Mutation

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

Frontotemporal lobar degeneration (FTLD) describes a group of neurodegenerative diseases that are frequent causes of dementia, accounting for 5% to 10% of all dementia patients and 10% to 20% of patients with onset of dementia before age 65. Frontotemporal dementia (FTD) is the most common clinical manifestation of FTLD. The clinical presentation of FTD is variable, but typically includes changes in personality and social conduct, often associated with disinhibition, followed by more general cognitive decline, eventually leading to dementia. The age of onset is extremely variable, ranging from 35 to 87 years. Duration of the disease ranges from 3 to 12 years.


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, with GRN located only 1.7 Mb centromeric of MAPT. GRN consists of 12 coding exons and 1 noncoding exon.


GRN encodes progranulin, a multifunctional protein that plays a role in multiple processes including development, wound repair, and inflammation. The function of GRN in the brain is not well understood, but progranulin is widely expressed in neurons and glial cells. More than 40 different pathogenic GRN mutations have been reported. All pathogenic mutations identified to date create functional null alleles that result in decreased progranulin production, suggesting that reduced levels of progranulin may lead to neurodegeneration.

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

Screening of at-risk individuals when a mutation in the GRN 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 #89188 Progranulin Gene (GRN), Full Gene Analysis.


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.


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, Hutton M: The genetics of frontotemporal lobar degeneration. Curr Neurol Neurosci Rep 2007 Sep;7(5):434-42

2. Gass J, Cannon A, Mackenzie IR, Boeve B, et al: Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Hum Molec Genet 2006 Oct 15;15(20):2988-3001

3. Cruts M, Gijselinck I, van der Zee J, et al: Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 2006 Aug 24, 442(7105):920-924

4. Eriksen JL, Mackenzie IR: Progranulin: normal function and role in neurodegeneration. J Neurochem 2008;104:287-297