Linked Life Data

17436289

Source:http://linkedlifedata.com/resource/pubmed/id/17436289

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-8-2
pubmed:abstractText
Frontotemporal dementia (FTD) is the second most frequent type of neurodegenerative dementias. Mutations in the progranulin gene (GRN, PGRN) were recently identified in FTDU-17, an FTD subtype characterized by ubiquitin-immunoreactive inclusions and linkage to chromosome 17q21. We looked for PGRN mutations in a large series of 210 FTD patients (52 familial, 158 sporadic) to accurately evaluate the frequency of PGRN mutations in both sporadic and familial FTD, and FTD with associated motoneuron disease (FTD-MND), as well as to study the clinical phenotype of patients with a PGRN mutation. We identified nine novel PGRN null mutations in 10 index patients. The relative frequency of PGRN null mutations in FTD was 4.8% (10/210) and 12.8% (5/39) in pure familial forms. Interestingly, 5/158 (3.2%) apparently sporadic FTD patients carried a PGRN mutation, suggesting the possibility of de novo mutations or incomplete penetrance. In contrast, none of the 43 patients with FTD-MND had PGRN mutations, supporting that FTDU-17 and FTD-MND are genetically distinct. The clinical phenotype of PGRN mutation carriers was particular because of the wide range in onset age and the frequent occurrence of early apraxia (50%), visual hallucinations (30%), and parkinsonism (30%) during the course of the disease. This study supports that PGRN null mutations represent a more frequent cause of FTD than MAPT mutations (4.8% vs. 2.9%) but are not responsible for FTD-MND. It also demonstrates that half of the patients with a PGRN mutation in our series had no apparent family history of dementia. Taking this into account, genetic testing should be now considered more systematically, even in patients without obvious familial history of FTD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1098-1004
pubmed:author
pubmed-author:BriceAlexisA, pubmed-author:CampionDominiqueD, pubmed-author:CamuzatAgnèsA, pubmed-author:CrutsMarcM, pubmed-author:De PooterTimT, pubmed-author:DidicMiraM, pubmed-author:DuboisBrunoB, pubmed-author:DuyckaertsCharlesC, pubmed-author:French Research Network on FTD/FTD-MND, pubmed-author:GijselinckIlseI, pubmed-author:GolfierVéroniqueV, pubmed-author:HannequinDidierD, pubmed-author:LacomblezLucetteL, pubmed-author:LaquerrièreAnnieA, pubmed-author:Le BerIsabelleI, pubmed-author:MichelBernard-FrançoisBF, pubmed-author:PuelMichèleM, pubmed-author:SalachasFrançoisF, pubmed-author:SellalFrançoisF, pubmed-author:Thomas-AntérionCatherineC, pubmed-author:Van BroeckhovenChristineC, pubmed-author:Van den BroeckMarleenM, pubmed-author:VercellettoMartineM, pubmed-author:VerpillatPatriceP, pubmed-author:van der ZeeJulieJ
pubmed:copyrightInfo
(c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
846-55
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Progranulin null mutations in both sporadic and familial frontotemporal dementia.
pubmed:affiliation
INSERM, UMR679, Paris, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't