{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:42:55Z","timestamp":1760985775369},"reference-count":8,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["HG 02449"],"award-info":[{"award-number":["HG 02449"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001671","name":"Hereditary Disease Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001671","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009836","name":"Huntington Society of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000887","name":"Huntington's Disease Society of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine phenotype\u2013genotype discrepancies (<jats:styled-content style=\"fixed-case\">PGD<\/jats:styled-content>s) wherein genotype\u2010concealed and prospective judgments of the motor onset of Huntington disease (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>) occurred among at\u2010risk adults who had nonexpanded (&lt;37) cytosine\u2013adenine\u2013guanine (<jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content>) trinucleotide <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> repeats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined the prospective clinical assessments of investigators who were kept unaware of individual <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content> lengths in the Prospective Huntington At\u2010Risk Observational Study (<jats:styled-content style=\"fixed-case\">PHAROS<\/jats:styled-content>) who enrolled and followed undiagnosed adults at risk for <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> who chose not to learn their gene status. Subjects (<jats:italic>n<\/jats:italic>\u00a0=\u00a01001) at 43 Huntington Study Group research sites in the <jats:styled-content style=\"fixed-case\">US<\/jats:styled-content> and Canada were evaluated prospectively and systematically between 1999 and 2009. At each site, an investigator was designated to perform comprehensive clinic assessments and another investigator to rate only the motor examination. Phenoconversion from a \u201cpremanifest\u201d status to a confidently \u201cmanifest\u201d status was based on investigator judgment (diagnostic confidence level) of the extrapyramidal motor features of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 20 <jats:styled-content style=\"fixed-case\">PGD<\/jats:styled-content>s that over time had less severe motor scores than the 101 phenoconversions with <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content> \u226537, but more severe motor scores than nonconversions. Following conversion, subjects with <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content> \u226537 expansions worsened more motorically and cognitively than <jats:styled-content style=\"fixed-case\">PGD<\/jats:styled-content> subjects in the\u00a0&lt;\u00a037 group. <jats:styled-content style=\"fixed-case\">PGD<\/jats:styled-content>s were concentrated among three sites and a few investigators, especially raters who only assessed the motor examination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The ability to detect the clinical onset of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> in a timely and reliable fashion remains the key for developing experimental treatments aimed at postponing the clinical onset of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>. Comprehensive clinical evaluation is a more accurate and reliable basis for determining <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> clinical onset than sole reliance on judging the extrapyramidal features of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.781","type":"journal-article","created":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T00:38:01Z","timestamp":1556757481000},"page":"1046-1052","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phenotype\u2013genotype discrepancies in the prospective Huntington at\u2010risk observational study"],"prefix":"10.1002","volume":"6","author":[{"given":"Ira","family":"Shoulson","sequence":"first","affiliation":[{"name":"University of Rochester Medical Center Rochester New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley","family":"Eberly","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center Rochester New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Oakes","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center Rochester New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"Kayson","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center Rochester New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne B.","family":"Young","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the PHAROS Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23685"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318294b304"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.7.991"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.2736"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870110204"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000479018"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.14com09235"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-0059"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.781","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.781","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.781","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T19:18:33Z","timestamp":1694373513000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":8,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/acn3.781"],"URL":"https:\/\/doi.org\/10.1002\/acn3.781","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"type":"print","value":"2328-9503"},{"type":"electronic","value":"2328-9503"}],"subject":[],"published":{"date-parts":[[2019,5]]},"assertion":[{"value":"2019-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}