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dc.contributor.authorLatourelle, Jeanne C.en_US
dc.contributor.authorSun, Meien_US
dc.contributor.authorLew, Mark F.en_US
dc.contributor.authorSuchowersky, Oksanaen_US
dc.contributor.authorKlein, Christineen_US
dc.contributor.authorGolbe, Lawrence I.en_US
dc.contributor.authorMark, Margery H.en_US
dc.contributor.authorGrowdon, John H.en_US
dc.contributor.authorWooten, G. Fredericken_US
dc.contributor.authorWatts, Ray L.en_US
dc.contributor.authorGuttman, Marken_US
dc.contributor.authorRacette, Brad A.en_US
dc.contributor.authorPerlmutter, Joel S.en_US
dc.contributor.authorAhmed, Anwaren_US
dc.contributor.authorShill, Holly A.en_US
dc.contributor.authorSinger, Carlosen_US
dc.contributor.authorGoldwurm, Stefanoen_US
dc.contributor.authorPezzoli, Giannien_US
dc.contributor.authorZini, Michelaen_US
dc.contributor.authorSaint-Hilaire, Marie H.en_US
dc.contributor.authorHendricks, Audrey E.en_US
dc.contributor.authorWilliamson, Sallyen_US
dc.contributor.authorNagle, Michael W.en_US
dc.contributor.authorWilk, Jemma B.en_US
dc.contributor.authorMassood, Tiffanyen_US
dc.contributor.authorHuskey, Karen W.en_US
dc.contributor.authorLaramie, Jason M.en_US
dc.contributor.authorDeStefano, Anita L.en_US
dc.contributor.authorBaker, Kenneth B.en_US
dc.contributor.authorItin, Iliaen_US
dc.contributor.authorLitvan, Ireneen_US
dc.contributor.authorNicholson, Garthen_US
dc.contributor.authorCorbett, Alastairen_US
dc.contributor.authorNance, Marthaen_US
dc.contributor.authorDrasby, Edwarden_US
dc.contributor.authorIsaacson, Stuarten_US
dc.contributor.authorBurn, David J.en_US
dc.contributor.authorChinnery, Patrick F.en_US
dc.contributor.authorPramstaller, Peter P.en_US
dc.contributor.authorAl-hinti, Jomanaen_US
dc.contributor.authorMoller, Anette T.en_US
dc.contributor.authorOstergaard, Karenen_US
dc.contributor.authorSherman, Scott J.en_US
dc.contributor.authorRoxburgh, Richarden_US
dc.contributor.authorSnow, Barryen_US
dc.contributor.authorSlevin, John T.en_US
dc.contributor.authorCambi, Francaen_US
dc.contributor.authorGusella, James F.en_US
dc.contributor.authorMyers, Richard H.en_US
dc.date.accessioned2011-12-29T22:21:02Z
dc.date.available2011-12-29T22:21:02Z
dc.date.copyright2008
dc.date.issued2008-11-5
dc.identifier.citationLatourelle, Jeanne C., Mei Sun, Mark F. Lew, Oksana Suchowersky, Christine Klein, Lawrence I. Golbe, Margery H. Mark, John H. Growdon, G. Frederick Wooten, Ray L. Watts, Mark Guttman, Brad A. Racette, Joel S. Perlmutter, Anwar Ahmed, Holly A. Shill, Carlos Singer, Stefano Goldwurm, Gianni Pezzoli, Michela Zini, Marie H. Saint-Hilaire, Audrey E. Hendricks, Sally Williamson, Michael W. Nagle, Jemma B. Wilk, Tiffany Massood, Karen W. Huskey, Jason M. Laramie, Anita L. DeStefano, Kenneth B. Baker, Ilia Itin, Irene Litvan, Garth Nicholson, Alastair Corbett, Martha Nance, Edward Drasby, Stuart Isaacson, David J. Burn, Patrick F. Chinnery, Peter P. Pramstaller, Jomana Al-hinti, Anette T. Moller, Karen Ostergaard, Scott J. Sherman, Richard Roxburgh, Barry Snow, John T. Slevin, Franca Cambi, James F. Gusella, Richard H. Myers. "The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study." BMC Medicine 6:32. (2008)
dc.identifier.issn1741-7015
dc.identifier.urihttps://hdl.handle.net/2144/2559
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.description.sponsorshipBumpus Foundation; Public Health Service (R01 NS36711-09); Italian Telethon (GTF04007)en_US
dc.language.isoen
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2008 Latourelle et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.titleThe Gly2019Ser Mutation in LRRK2 Is not Fully Penetrant in Familial Parkinson's Disease: The GenePD Studyen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/1741-7015-6-32
dc.identifier.pmid18986508
dc.identifier.pmcid2596771


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Copyright 2008 Latourelle et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2008 Latourelle et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.