{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:13:22Z","timestamp":1790630002242,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T00:00:00Z","timestamp":1453248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The Klinefelter syndrome (<jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content>) is the most frequent sex chromosomal disorder in males, characterized by at least one supernumerary X chromosome (most frequent karyotype 47,<jats:styled-content style=\"fixed-case\">XXY<\/jats:styled-content>). This syndrome presents with a broad range of phenotypes. The common characteristics include small testes and infertility, but <jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content> subjects are at increased risk of hypogonadism, cognitive dysfunction, obesity, diabetes, metabolic syndrome, osteoporosis, and autoimmune disorders, which are present in variable proportion. Although part of the clinical variability might be linked to a different degree of testicular function observed in <jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content> patients, genetic mechanisms of the supernumerary X chromosome might contribute. Gene\u2010dosage effects and parental origin of the supernumerary X chromosome have been suggested to this regard. No study has been performed analyzing the genetic constitution of the X chromosome in terms of copy number variations (<jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s) and their possible involvement in phenotype of <jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content>. To this aim, we performed a <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> arrays analysis on 94 <jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content> and 85 controls. We found that <jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content> subjects have more frequently than controls X\u2010linked <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s (39\/94, [41.5%] with respect to 12\/42, [28.6%] of females, and 8\/43, [18.6%] of males, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01). The number of X\u2010linked <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s in <jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content> patients was 4.58\u00a0\u00b1\u00a01.92 <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s\/subject, significantly higher with respect to that found in control females (1.50\u00a0\u00b1\u00a01.29 <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s\/subject) and males (1.14\u00a0\u00b1\u00a00.37 <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s\/subject). Importantly, 94.4% X\u2010linked <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s in <jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content> subjects were duplications, higher with respect to control males (50.0%, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001) and females (83.3%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.1). Half of the X\u2010linked <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s fell within regions encompassing genes and most of them (90%) included genes escaping X\u2010inactivation in the regions of X\u2013Y homology, particularly in the pseudoautosomal region 1 (<jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>1) and Xq21.31. This study described for the first time the genetic properties of the X chromosome in <jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content> and suggests that X\u2010linked <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s (especially duplications) might contribute to the clinical phenotype.<\/jats:p>","DOI":"10.1111\/andr.12146","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T21:19:30Z","timestamp":1453324770000},"page":"328-334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The Klinefelter syndrome is associated with high recurrence of copy number variations on the X chromosome with a potential role in the clinical phenotype"],"prefix":"10.1111","volume":"4","author":[{"given":"M. S.","family":"Rocca","sequence":"first","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine Department of Medicine University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Pecile","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS \u201cBurlo Garofolo\u201d Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Cleva","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS \u201cBurlo Garofolo\u201d Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Speltra","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine Department of Medicine University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Selice","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine Department of Medicine University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Di Mambro","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine Department of Medicine University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Foresta","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine Department of Medicine University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ferlin","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine Department of Medicine University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2002.01504.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31349"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-006-9330-0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003350010177"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpuro0775"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000074209.17561.99"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.05.006"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3687"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2218"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2012.01269.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-74"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181ed6185"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6408(1998)23:3<215::AID-DVG7>3.0.CO;2-X"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-001-0609-y"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000076532"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/08977190410001720879"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1876528900902010020"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044887"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0134-0"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920207780368141"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0004-27302008000800013"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.8.2927"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12042"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5320-z"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33118"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30339"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji240"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dem358"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32914"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genm.2012.01.005"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.12229_suppl"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaq019"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.27806"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-1-42"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2780"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fandr.12146","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fandr.12146","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T08:06:28Z","timestamp":1695456388000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.12146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,20]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1111\/andr.12146"],"URL":"https:\/\/doi.org\/10.1111\/andr.12146","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,20]]},"assertion":[{"value":"2015-09-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}