FRONTOTEMPORAL DEMENTIA (FTD) - PGRN GENE
Gene Symbol: PGRN
Chromosomal Locus: 17q21
Pseudonyms: Ubiquitin-positive Frontotemporal Dementia, FTD-PGRN, Granulin, GRN
TURNAROUND TIME: 4 weeks
Polymerase chain reaction (PCR) followed by sequencing all 12 exons (coding and splicing regions) of the PGRN gene.
- Collect: Prefer two 5ml whole blood EDTA (lavender top) tube.
- Min. Collection: 0.7 ml whole blood EDTA.
- Transport: blood EDTA at Room Temp shipped regular next day air (No Saturday delivery; store specimen at 4°C and ship Monday).
- Stability: Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen: unacceptable
- Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood.
- Prenatal testing: Direct: 5ml direct unspun amniotic fluid or 15mg CVS tissue with a backup flask growing. Culture: confluent T25 flask. Maternal blood sample is required for maternal cell contamination studies.
Counseling and informed consent are recommended for genetic testing. A consent form
is available as a resource but not required.
Incidence: Unknown. However, frontotemporal dementia (FTD) is the second most common form of dementia. 50-70% of FTD is a result of the PGRN gene. In the remainder, (20-50%), the defective gene is MAPT.
Inheritance: Autosomal dominant.
Disease Characteristics: Behavioral and personality changes leading to cognitive decline, dementia and motor abnormalities. PGRN-related FTD is distinct by the fact that there are ubiquitin-associated inclusions rather than the tau deposits associated with MAPT.
Molecular Genetic Mechanism: A variety of mutations have been cited throughout the entire gene.
Clinical Sensitivity: GRN mutations are present in 5-10% of all FTD and in 25% of familial FTD, the assay will detect 90% of those mutations.
Analytical Sensitivity: 99%.
Test Limitations: Mutations that are not in the coding sequence of the PGRN gene will not be detected. Rare diagnostic errors can occur due to primer / probe site mutations or rare polymorphisms.
Indications for Use:
- To confirm the nature of the dementia in an affected individual and determine inheritance risks.
- Presymptomatic testing for a known familial mutation.