Sorted By Test Name - Mayo Medical Laboratories

GRNKM
89187
PINS
neurodegeneration.
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
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 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, 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
Progranulin Gene (GRN), Known Mutation
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
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: Screening of at-risk individuals when a mutation in the GRN gene has been identified in
an affected family member
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 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
Proinsulin, Plasma
80908
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