Guven, G;
Bilgic, B;
Tufekcioglu, Z;
Erginel Unaltuna, N;
Hanagasi, H;
Gurvit, H;
Singleton, A;
... Lohmann, E; + view all
(2019)
Peripheral GRN mRNA and Serum Progranulin Levels as a Potential Indicator for Both the Presence of Splice Site Mutations and Individuals at Risk for Frontotemporal Dementia.
Journal of Alzheimer's Disease
, 67
(1)
pp. 159-167.
10.3233/JAD-180599.
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Abstract
Progranulin (GRN) gene mutations are a major cause of frontotemporal dementia (FTD). Most mutations identified to date are null mutations, which are predicted to cause the pathology via haploinsufficiency. Decreased peripheral progranulin protein (PGRN) levels are associated with the presence of GRN null mutations and are accepted as reliable biomarkers. In this study, our aim was to test whether the presence of specific GRN splice site mutations (c.– 8+2T>G and c.708+6_9del), could be predicted by peripheral mRNA or protein GRN levels, by studying affected and asymptomatic individuals from FTD families. We also tested four missense GRN variants to assess if altered GRN levels depended on the type of mutation. Our results confirmed a reduction in both mRNA and protein PGRN levels in the splice site mutation carriers, which is consistent with previous reports for null mutations. Our results also suggested that both decreased peripheral GRN mRNA and serum PGRN levels indicate the presence of pathogenic mutations in affected individuals, and identify the asymptomatic individuals at risk, without previous knowledge of genetic status. Both inferences suggest a potential use of peripheral GRN mRNA or serum PGRN levels as biomarkers for families with FTD.
| Type: | Article |
|---|---|
| Title: | Peripheral GRN mRNA and Serum Progranulin Levels as a Potential Indicator for Both the Presence of Splice Site Mutations and Individuals at Risk for Frontotemporal Dementia |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JAD-180599 |
| Publisher version: | http://dx.doi.org/10.3233/JAD-180599 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | ELISA, frontotemporal dementia, progranulin, serum, splice site mutation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10068237 |
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