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dc.contributor.authorLatourelle, Jeanne C
dc.contributor.authorLew, Mark F
dc.contributor.authorSuchowersky, Oksana
dc.contributor.authorKlein, Christine
dc.contributor.authorGolbe, Lawrence I
dc.contributor.authorMark, Margery H
dc.contributor.authorWooten, G Frederick
dc.contributor.authorWatts, Ray L
dc.contributor.authorGuttman, Mark
dc.contributor.authorRacette, Brad A
dc.contributor.authorPerlmutter, Joel S
dc.contributor.authorAhmed, Anwar
dc.contributor.authorShill, Holly A
dc.contributor.authorSinger, Carlos
dc.contributor.authorGoldwurm, Stefano
dc.contributor.authorPezzoli, Gianni
dc.contributor.authorZini, Michela
dc.contributor.authorSaint-Hilaire, Marie H
dc.contributor.authorHendricks, Audrey E
dc.contributor.authorWilliamson, Sally
dc.contributor.authorNagle, Michael W
dc.contributor.authorWilk, Jemma B
dc.contributor.authorMassood, Tiffany
dc.contributor.authorHuskey, Karen W
dc.contributor.authorLaramie, Jason M
dc.contributor.authorDeStefano, Anita L
dc.contributor.authorBaker, Kenneth B
dc.contributor.authorItin, Ilia
dc.contributor.authorLitvan, Irene
dc.contributor.authorNicholson, Garth
dc.contributor.authorCorbett, Alastair
dc.contributor.authorNance, Martha
dc.contributor.authorDrasby, Edward
dc.contributor.authorIsaacson, Stuart
dc.contributor.authorBurn, David J
dc.contributor.authorChinnery, Patrick F
dc.contributor.authorPramstaller, Peter P
dc.contributor.authorAl-hinti, Jomana
dc.contributor.authorMoller, Anette T
dc.contributor.authorOstergaard, Karen
dc.contributor.authorRoxburgh, Richard
dc.contributor.authorSnow, Barry
dc.contributor.authorSlevin, John T
dc.contributor.authorCambi, Franca
dc.contributor.authorGrowdon, John Herbert
dc.contributor.authorGusella, James Francis
dc.contributor.authorSun, Mei
dc.contributor.authorSherman, Scott J
dc.contributor.authorMyers, Richard Hepworth
dc.date.accessioned2011-04-23T14:58:07Z
dc.date.issued2008
dc.identifier.citationLatourelle, Jeanne C., Mei Sun, Mark F. Lew, Oksana Suchowersky, Christine Klein, Lawrence I. Golbe, Margery H. Mark, et al. 2008. The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study. BMC Medicine 6: 32.en_US
dc.identifier.issn1741-7015en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4874792
dc.description.abstractBackground: We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD. Methods: A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample. Results: Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 LRRK2 mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families. Conclusion: Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility factors may also increase the risk of non-LRRK2-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for LRRK2 carriers are independent of the factors which increase PD prevalence in men.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/1741-7015-6-32en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596771/pdf/en_US
dash.licenseLAA
dc.titleThe Gly2019Ser Mutation in LRRK2 is not Fully Penetrant in Familial Parkinson's Disease: The GenePD Studyen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBMC Medicineen_US
dash.depositing.authorGrowdon, John Herbert
dc.date.available2011-04-23T14:58:07Z
dash.affiliation.otherHMS^Neurology-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Geneticsen_US
dc.identifier.doi10.1186/1741-7015-6-32*
dash.authorsorderedfalse
dash.contributor.affiliatedSun, Mei
dash.contributor.affiliatedGusella, James
dash.contributor.affiliatedMyers, Richard Hepworth
dash.contributor.affiliatedGrowdon, John


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