Gene expression study on peripheral blood identifies progranulin mutations

• Published in: Annals of neurology Vol. 64; no. 1; pp. 92 - 96
• Main Authors: Coppola, Giovanni, Karydas, Anna, Rademakers, Rosa, Wang, Qing, Baker, Matt, Hutton, Mike, Miller, Bruce L., Geschwind, Daniel H.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2008; Willey-Liss
• Subjects: Adult; Aged; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia - blood; Dementia - diagnosis; Dementia - genetics; DNA Mutational Analysis; Down-Regulation - genetics; Female; Gene Expression; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Genetic Testing; Humans; Intercellular Signaling Peptides and Proteins - analysis; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - genetics; Leukocytes - metabolism; Medical sciences; Middle Aged; Mutation - genetics; Neurodegenerative Diseases - blood; Neurodegenerative Diseases - diagnosis; Neurodegenerative Diseases - genetics; Neurology; Predictive Value of Tests; Progranulins; RNA, Messenger - analysis; RNA, Messenger - blood; Gene expression; Nervous system diseases; Mutation
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.21397

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. Ann Neurol 2008.