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Title
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Granulin mutations associated with frontotemporal lobar degeneration and related disorders: an update
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Human mutation. - New York, N.Y.
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Publication
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New York, N.Y.
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2008
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ISSN
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1059-7794
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DOI
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10.1002/HUMU.20785
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Volume/pages
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29
:12
(2008)
, p. 1373-1386
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ISI
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000261671200001
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Full text (Publisher's DOI)
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