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Test ID: GRNZ Progranulin Gene (GRN), Full Gene Analysis

Useful For

Aiding the diagnosis of frontotemporal dementia

 

Distinguishing frontotemporal dementia from other dementias, including Alzheimer dementia

 

Identifying individuals who are at increased risk of frontotemporal dementia

Method Name

Polymerase Chain Reaction (PCR)/DNA Sequencing Analysis

Reporting Name

Progranulin Gene Full Gene Analysis

Specimen Type

Varies


Shipping Instructions


Specimen preferred to arrive within 96 hours of draw.



Specimen Required


Patient Preparation: 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.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

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 impulse 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 and 1 noncoding exons.

 

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.

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Rademakers R, Hutton M: The genetics of frontotemporal lobar degeneration. Curr Neurol Neurosci Rep. 2007 Sep;7(5):434-442

3. Gass J, Cannon A, Mackenzie IR, 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

4. 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

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

Day(s) and Time(s) Performed

Performed weekly, varies

Analytic Time

14 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81406 GRN (granulin) (eg, frontotemporal dementia), full gene sequence

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GRNZ Progranulin Gene Full Gene Analysis In Process

 

Result ID Test Result Name Result LOINC Value
53936 Result Summary 50397-9
53937 Result No LOINC Needed
53938 Interpretation 69047-9
53939 Additional Information 48767-8
53940 Specimen 31208-2
53941 Source 31208-2
53942 Released By No LOINC Needed

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

2. Molecular Genetics: Neurology Patient Information in Special Instructions

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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