{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:31:04Z","timestamp":1777552264420,"version":"3.51.4"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2013,7,22]],"date-time":"2013-07-22T00:00:00Z","timestamp":1374451200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0068951","type":"journal-article","created":{"date-parts":[[2013,7,22]],"date-time":"2013-07-22T21:08:54Z","timestamp":1374527334000},"page":"e68951","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["The V471A Polymorphism in Autophagy-Related Gene ATG7 Modifies Age at Onset Specifically in Italian Huntington Disease Patients"],"prefix":"10.1371","volume":"8","author":[{"given":"Silke","family":"Metzger","sequence":"first","affiliation":[]},{"given":"Carolin","family":"Walter","sequence":"additional","affiliation":[]},{"given":"Olaf","family":"Riess","sequence":"additional","affiliation":[]},{"given":"Raymund A. C.","family":"Roos","sequence":"additional","affiliation":[]},{"given":"J\u00f8rgen E.","family":"Nielsen","sequence":"additional","affiliation":[]},{"given":"David","family":"Craufurd","sequence":"additional","affiliation":[]},{"name":"REGISTRY Investigators of the European Huntington\u2019s Disease Network","sequence":"additional","affiliation":[]},{"given":"Huu Phuc","family":"Nguyen","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2013,7,22]]},"reference":[{"key":"ref1","unstructured":"Bates G, Harper P, Jones L (2002) Huntington\u2019s disease. 3. Oxford: Oxford University press."},{"key":"ref2","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/ng0893-398","article-title":"The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington\u2019s disease","volume":"4","author":"SE Andrew","year":"1993","journal-title":"Nat Genet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/ng0893-387","article-title":"Trinucleotide repeat length instability and age of onset in Huntington\u2019s disease","volume":"4","author":"M Duyao","year":"1993","journal-title":"Nat Genet"},{"key":"ref4","first-page":"971","article-title":"A novel gene containing a trinucleotide repeat that is unstable on Huntington\u2019s disease chromosomes","volume":"26","year":"1993","journal-title":"Cell"},{"key":"ref5","first-page":"1202","article-title":"The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size","volume":"60","author":"RR Brinkman","year":"1997","journal-title":"Am J Hum Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/BF00209410","article-title":"Confidence intervals for predicted age of onset, given the size of (CAG)n repeat, in Huntington\u2019s disease","volume":"95","author":"G Lucotte","year":"1995","journal-title":"Hum Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1002\/mds.23108","article-title":"A retrospective study of the impact of lifestyle on age at onset of Huntington disease","volume":"25(10)","author":"MK Trembath","year":"2010","journal-title":"Mov Disord"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1073\/pnas.94.8.3872","article-title":"Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington disease","volume":"94(8)","author":"DC Rubinsztein","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1212\/WNL.53.6.1330","article-title":"Evidence for the GluR6 gene associated with younger onset age of Huntington\u2019s disease","volume":"53(6)","author":"ME MacDonald","year":"1999","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10048-004-0198-8","article-title":"NR2A and NR2B receptor gene variations modify age at onset in Huntington disease","volume":"6(1)","author":"L Arning","year":"2005","journal-title":"Neurogenetics"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"RRN1247","DOI":"10.1371\/currents.RRN1247","article-title":"NMDA receptor gene variations as modifiers in Huntington disease: a replication study","volume":"3","author":"C Saft","year":"2011","journal-title":"PLoS Curr"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1093\/hmg\/ddn003","article-title":"Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington\u2019s disease","volume":"17(8)","author":"S Metzger","year":"2008","journal-title":"Hum Mol Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1073\/pnas.98.4.1811","article-title":"The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: neuropathologic and genetic evidence for a role in Huntington\u2019s disease pathogenesis","volume":"98(4)","author":"S Holbert","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.neulet.2004.10.018","article-title":"Modulation of age at onset of Huntington disease patients by variations in TP53 and human caspase activated DNase (hCAD) genes","volume":"374(2)","author":"B Chattopadhyay","year":"2005","journal-title":"Neurosci Lett"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1750-1326-4-10","article-title":"PGC-1alpha as modifier of onset age in Huntington disease","volume":"4","author":"E Taherzadeh-Fard","year":"2009","journal-title":"Mol Neurodegener"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1750-1326-4-3","article-title":"The gene coding for PGC-1alpha modifies age at onset in Huntington\u2019s Disease","volume":"4","author":"P Weydt","year":"2009","journal-title":"Mol Neurodegener"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1326-6-1","article-title":"Localization of sequence variations in PGC-1\u03b1 influence their modifying effect in Huntington disease","volume":"6(1)","author":"HV Che","year":"2011","journal-title":"Mol Neurodegener"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0304-3940(02)00231-8","article-title":"Mutation analysis and association studies of the ubiquitin carboxy-terminal hydrolase L1 gene in Huntington\u2019s disease","volume":"328(1)","author":"P Naz\u00e9","year":"2002","journal-title":"Neurosci Lett"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10048-005-0023-z","article-title":"The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington\u2019s disease","volume":"7(1)","author":"S Metzger","year":"2006","journal-title":"Neurogenetics"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00439-010-0873-9","article-title":"Age at onset in Huntington\u2019s disease is modified by the autophagy pathway: implication of the V471A polymorphism in Atg7","volume":"128(4)","author":"S Metzger","year":"2010","journal-title":"Hum Genet"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2217\/fnl.11.65","article-title":"Genetic modifiers of Huntington\u2019s disease: beyond CAG","volume":"7","author":"L Arning","year":"2012","journal-title":"Future Neurol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.cellbio.15.1.1","article-title":"Vacuolar import of proteins and organelles from the cytoplasm","volume":"15","author":"DJ Klionsky","year":"1999","journal-title":"Annu Rev Cell Dev Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/hmg\/11.9.1107","article-title":"Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy","volume":"11(9)","author":"B Ravikumar","year":"2002","journal-title":"Hum Mol Genet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1093\/hmg\/11.22.2689","article-title":"Aggregate formation inhibits proteasomal degradation of polyglutamine proteins","volume":"11(22)","author":"LG Verhoef","year":"2002","journal-title":"Hum Mol Genet"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1083\/jcb.200412022","article-title":"Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice","volume":"169(3)","author":"M Komatsu","year":"2005","journal-title":"J Cell Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nature04723","article-title":"Loss of autophagy in the central nervous system causes neurodegeneration in mice","volume":"441(7095)","author":"M Komatsu","year":"2006","journal-title":"Nature"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/ng1362","article-title":"Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease","volume":"36(6)","author":"B Ravikumar","year":"2004","journal-title":"Nat Genet"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1083\/jcb.200504035","article-title":"Lithium induces autophagy by inhibiting inositol monophosphatase","volume":"170(7)","author":"S Sarkar","year":"2005","journal-title":"J Cell Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1136\/jnnp.2010.209668","article-title":"Observing Huntington\u2019s disease: the European Huntington\u2019s Disease Network\u2019s REGISTRY","volume":"82(12)","author":"M Orth","year":"2011","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s004390100505","article-title":"Nomenclature for the description of human sequence variations","volume":"109(1)","author":"JT den Dunnen","year":"2001","journal-title":"Hum Genet"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/hmg\/3.1.93","article-title":"Analysis of the trinucleotide repeat expansion in Italian families affected with Huntington disease","volume":"3(1)","author":"A Novelletto","year":"1994","journal-title":"Hum Mol Genet"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/hmg\/2.10.1547","article-title":"Correlation between the onset age of Huntington\u2019s disease and length of the trinucleotide repeat in IT-15","volume":"2(10)","author":"OC Stine","year":"1993","journal-title":"Hum Mol Genet"},{"key":"ref33","first-page":"3498","article-title":"Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington\u2019s disease age of onset","volume":"9","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/ajmg.1400","article-title":"Familial influence on age of onset among siblings with Huntington\u2019s disease","volume":"105","author":"A Rosenblatt","year":"2001","journal-title":"Am J Med Genet"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1086\/378133","article-title":"A genome scan for modifiers of age at onset in Huntington disease: the HD MAPS study","volume":"73","author":"JL Li","year":"2003","journal-title":"Am J Hum Genet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1212\/01.wnl.0000175977.57661.b1","article-title":"Association between BDNF Val66Met polymorphism and age at onset in Huntington disease","volume":"65(6)","author":"J Alberch","year":"2005","journal-title":"Neurology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.nbd.2006.07.002","article-title":"No evidence of association between BDNF gene variants and age-at-onset of Huntington\u2019s disease","volume":"24(2)","author":"E Di Maria","year":"2006","journal-title":"Neurobiol Dis"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.nbd.2006.07.008","article-title":"Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington\u2019s disease","volume":"24(2)","author":"S Kishikawa","year":"2006","journal-title":"Neurobiol Dis"},{"key":"ref39","first-page":"44","article-title":"Replication of twelve association studies for Huntington\u2019s disease residual age of onset in large Venezuelan kindreds","volume":"44(1)","author":"JM Andresen","year":"2007","journal-title":"J Med Genet"},{"key":"ref40","first-page":"404","article-title":"TAA repeat variation in the GRIK2 gene does not influence age at onset in Huntington\u2019s disease","volume":"424(3)","author":"JH Lee","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00439-006-0221-2","article-title":"Genetic analysis of candidate genes modifying the age-at-onset in Huntington\u2019s disease","volume":"120(2)","author":"S Metzger","year":"2006","journal-title":"Hum Genet"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1002\/mds.23849","article-title":"CAG repeat size in the normal HTT allele and age of onset in Huntington\u2019s disease","volume":"26(13)","author":"NA Aziz","year":"2011","journal-title":"Mov Disord"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/ajmg.a.20190","article-title":"Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease","volume":"119A(3)","author":"L Djouss\u00e9","year":"2003","journal-title":"Am J Med Genet A"},{"key":"ref44","first-page":"108","article-title":"Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length","volume":"36(2)","author":"P Kehoe","year":"1999","journal-title":"J Med Genet"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/mds.23436","article-title":"The number of CAG repeats within the normal allele does not influence the age of onset in Huntington\u2019s disease","volume":"26(1)","author":"J Klemp\u00ed\u0159","year":"2011","journal-title":"Mov Disord"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1111\/j.1468-1331.2009.02706.x","article-title":"BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson\u2019s disease","volume":"16(11)","author":"FR Guerini","year":"2009","journal-title":"Eur J Neurol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1016\/j.jocn.2011.03.015","article-title":"Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with Parkinson\u2019s disease in a Greek population","volume":"18(12)","author":"C Karakasis","year":"2011","journal-title":"J Clin Neurosci"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/ana.10585","article-title":"Lack of association between the BDNF Val66Met polymorphism and Parkinson\u2019s disease in a Swedish population","volume":"53(6)","author":"A H\u00e5kansson","year":"2003","journal-title":"Ann Neurol"},{"key":"ref49","first-page":"12","article-title":"No association between the brain-derived neurotrophic factor 196 G&gt;A or 270 C&gt;T polymorphisms and Alzheimer\u2019s or Parkinson\u2019s disease","volume":"44(1)","author":"MS Saarela","year":"2006","journal-title":"Folia Neuropathol"},{"key":"ref50","first-page":"682","article-title":"A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study","volume":"73(3)","author":"JL Li","year":"2003","journal-title":"Am J Hum Genet"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1471-2350-7-71","article-title":"Genome-wide significance for a modifier of age at neurological onset in Huntington\u2019s disease at 6q23\u201324: the HD MAPS study","volume":"7","author":"JL Li","year":"2006","journal-title":"BMC Med Genet"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/gepi.20317","article-title":"Genomewide linkage scan reveals novel loci modifying age of onset of Huntington\u2019s disease in the Venezuelan HD kindreds","volume":"32(5)","author":"J Gay\u00e1n","year":"2008","journal-title":"Genet Epidemiol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1007\/s00439-012-1205-z","article-title":"Population stratification may bias analysis of PGC-1\u03b1 as a modifier of age at Huntington disease motor onset","volume":"131(12)","author":"EM Ramos","year":"2012","journal-title":"Hum Genet"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0068951","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T23:31:16Z","timestamp":1540337476000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0068951"}},"subtitle":[],"editor":[{"given":"Xiao-Jiang","family":"Li","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2013,7,22]]},"references-count":53,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2013,7,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0068951","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,22]]}}}