Publication
Title
Granulin mutations associated with frontotemporal lobar degeneration and related disorders: an update
Author
Abstract
Mutations in the gene encoding granulin (HUGO gene symbol GRN, also referred to as progranulin, PGRN), located at chromosome 17q21, were recently linked to tau-negative ubiquitin-positive frontotemporal lobar degeneration (FTLDU). Since then, 63 heterozygous mutations were identified in 163 families worldwide, all leading to loss of functional GRN, implicating a haploinsufficiency mechanism. Together, these mutations explained 5 to 10% of FTLD. The high mutation frequency, however, might still be an underestimation because not all patient samples were examined for all types of loss-of-function mutations and because several variants, including missense mutations, have a yet uncertain pathogenic significance. Although the complete phenotypic spectrum associated with GRN mutations is not yet fully characterized, it was shown that it is highly heterogeneous, suggesting the influence of modifying factors. A role of GRN in neuronal survival was suggested but the exact mechanism by which neurodegeneration and deposition of pathologic brain inclusions occur still has to be clarified.
Language
English
Source (journal)
Human mutation. - New York, N.Y.
Publication
New York, N.Y. : 2008
ISSN
1059-7794
Volume/pages
29:12(2008), p. 1373-1386
ISI
000261671200001
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.12.2008
Last edited 17.06.2017
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