Frontotemporal Dementia (FTD) - PGRN Gene

FRONTOTEMPORAL DEMENTIA (FTD) - PGRN GENE

Gene Symbol: PGRN

Chromosomal Locus: 17q21

Protein: Progranulin

Pseudonyms: Ubiquitin-positive Frontotemporal Dementia, FTD-PGRN, Granulin, GRN

TURNAROUND TIME: 4 weeks

TESTING METHODOLOGY:

Polymerase chain reaction (PCR) followed by sequencing all 12 exons (coding and splicing regions) of the PGRN gene.

SPECIMEN REQUIREMENTS:

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.

A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 to obtain further information.

Note: Counseling and informed consent are recommended for genetic testing. A consent form is available as a resource but not required.

INTERPRETATIVE DATA:

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.

Related Tests: MAPT Complete 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: