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.
ELISA
frontotemporal dementia
progranulin
serum
splice site mutation
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2019
2019
Historique:
pubmed:
27
11
2018
medline:
3
3
2020
entrez:
27
11
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30475763
pii: JAD180599
doi: 10.3233/JAD-180599
pmc: PMC6422018
mid: NIHMS1010955
doi:
Substances chimiques
Biomarkers
0
GRN protein, human
0
Progranulins
0
RNA Splice Sites
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
159-167Subventions
Organisme : Medical Research Council
ID : MR/K01417X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1001253
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L501542/1
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z99 AG999999
Pays : United States
Organisme : Parkinson's UK
ID : G-0907
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J004758/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701075
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901254
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N026004/1
Pays : United Kingdom
Organisme : Parkinson's UK
ID : G-1307
Pays : United Kingdom
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