Gene expression study on peripheral blood identifies progranulin mutations.
Peripheral blood is a readily available tissue source allowing relatively noninvasive screening for a host of medical conditions. We screened total-blood progranulin (PGRN) levels in 107 patients with neurodegenerative dementias and related conditions, and 36 control subjects, and report the following findings: (1) confirmation of high progranulin expression levels in peripheral blood; (2) two subjects with reduced progranulin levels and mutations in the PGRN gene confirmed by direct sequencing; and (3) greater PGRN messenger RNA levels in patients with clinical diagnosis of Alzheimer's disease. This proof-of-principle report supports the use of gene quantification as diagnostic screen for PGRN mutations and suggests a potential role for progranulin in Alzheimer's disease.
Coppola
Giovanni
G
Department of Neurology, Program in Neurogenetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Karydas
Anna
A
Rademakers
Rosa
R
Wang
Qing
Q
Baker
Matt
M
Hutton
Mike
M
Miller
Bruce L
BL
Geschwind
Daniel H
DH
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis; D003704:Dementia / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000097:blood / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D011237:Predictive Value of Tests; D000077153:Progranulins; D012333:RNA, Messenger / Q000032:analysis / Q000097:blood
C492314:GRN protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D012333:RNA, Messenger