Gene expression study on peripheral blood identifies progranulin mutations

Ann Neurol. 2008 Jul;64(1):92-6. doi: 10.1002/ana.21397.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics
  • DNA Mutational Analysis
  • Dementia / blood
  • Dementia / diagnosis
  • Dementia / genetics*
  • 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
  • Middle Aged
  • Mutation / genetics
  • Neurodegenerative Diseases / blood
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / genetics*
  • Predictive Value of Tests
  • Progranulins
  • RNA, Messenger / analysis
  • RNA, Messenger / blood

Substances

  • GRN protein, human
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • RNA, Messenger