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

Gene Expression Study on Peripheral Blood Identifies Progranulin Mutations

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Free PMC article

Gene Expression Study on Peripheral Blood Identifies Progranulin Mutations

Giovanni Coppola et al. Ann Neurol. .
Free PMC article

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.

Figures

Fig 1
Fig 1
Peripheral blood PGRN expression levels in 142 subjects. Data are expressed in log2-transformed normalized expression values. Dotted lines indicate two and three standard deviations (SDs) from the overall mean. Two samples (arrows) were outliers lying at approximately three SDs below the mean, corresponding to approximately 50% of reference progranulin messenger RNA levels. Blue denotes Alzheimer's disease patients; gray, amyotrophic lateral sclerosis patients; black, control subjects; green, corticobasal syndrome; red, frontotemporal lobar degeneration patients; and orange, progressive supranuclear palsy.
Fig 2
Fig 2
(A) Electropherograms showing two detected mutations: IVS7-1G>C or c.836-1G>>C (top) and c.675_676delCA (bottom). (B) Venn diagrams representing the number of genes differentially expressed in 2 subjects with PGRN mutations (412 genes; left circle) and in 41 frontotemporal lobar degeneration (FTLD) cases (143 genes; right circle) versus control subjects. The numbers of genes are in parentheses. There are 23,802 (bottom right corner) remaining genes on the array.
Fig 3
Fig 3
Box plot of log2-normalized PGRN expression levels in Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), and corticobasal syndrome (CBS) patients, and control subjects. (A) Analysis on all the subjects. (B) Analysis after exclusion of six outliers. *p ≤ 0.004; **p ≤ 0.001.

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