Granulin mutations associated with frontotemporal lobar degeneration and related disorders: an update.
Hum Mutat
; 29(12): 1373-86, 2008 Dec.
Article
in En
| MEDLINE
| ID: mdl-18543312
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dementia
/
Intercellular Signaling Peptides and Proteins
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Humans
/
Middle aged
Language:
En
Journal:
Hum Mutat
Journal subject:
GENETICA MEDICA
Year:
2008
Document type:
Article
Affiliation country: