{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T20:51:57Z","timestamp":1740171117542,"version":"3.37.3"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,7,12]],"date-time":"2018-07-12T00:00:00Z","timestamp":1531353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007353","name":"Fondation J\u00e9r\u00f4me Lejeune","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003483","name":"Hebrew University of Jerusalem","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Prader\u2010Willi syndrome (<jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content>) is a multisystem genetic disorder characterized by lack of satiety leading to morbid obesity, variable degrees of mental retardation, behavior disorders, short stature, and hypogonadism. The underlying genetic cause for <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content> is an imprinting defect resulting from a lack of expression of several paternally inherited genes embedded within the 15q11.2\u2010q13 region. Although the clinical expression of hypogonadism in <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content> is variable, there are no known cases of fertility in <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content> men. In this paper, we described a pure, nearly diploid seminoma in an apparently 32\u00a0year\u2010old infertile man with <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content> due to maternal uniparental disomy (UPD) on chromosome 15. The development of a germ cell tumor in this subject was an unanticipated result. The aim of this study was to explore the origin of the germ cell tumor in this <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content> male patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To explain the origin of the germ cell tumor (seminoma) in our <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content> patient we have characterized the tumor for cell morphology and tumor type by pathological examination (H&amp;E and immuno\u2010stainings), evaluated its karyotype by chromosomal microarray analysis and confirmed its <jats:styled-content style=\"fixed-case\">UPD<\/jats:styled-content> origin by haplotype analysis. In addition, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation status of the <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content>\u2010 and H19\u2010 imprinting centers in wild\u2010type and affected fibroblasts, patient derived induced pluripotent stem cells (<jats:styled-content style=\"fixed-case\">iPSC<\/jats:styled-content>s), and <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content> seminoma were determined by bisulfite <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> colony sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>To explain the apparent contradiction between the existence of a germ cell tumor and hypogonadism we first confirmed the germ cell origin of the tumor. Next, we determined the tumor chromosomal composition, and validated the presence of a maternal <jats:styled-content style=\"fixed-case\">UPD<\/jats:styled-content> in all examined cell types from this patient. Finally, we characterized the maternal imprints in the <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content> and H19 imprinting centers in the tumor and compared them with patient's fibroblasts and <jats:styled-content style=\"fixed-case\">iPSC<\/jats:styled-content>s derived from them. Unpredictably, methylation was reduced to 50% in the tumor, while preserved in the other cell types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We infer from this assay that the loss of methylation in the <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content> specifically in the tumor of our patient is most likely a locus\u2010specific event resulting from imprint relaxation rather than from general resetting of the imprints throughout the genome during germ line specification.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.448","type":"journal-article","created":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T04:38:48Z","timestamp":1531456728000},"page":"811-818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Incomplete methylation of a germ cell tumor (Seminoma) in a Prader\u2010Willi male"],"prefix":"10.1002","volume":"6","author":[{"given":"Talia","family":"Eldar\u2010Geva","sequence":"first","affiliation":[{"name":"Reproductive Endocrinology and Genetics Unit Department of Obstetrics and Gynecology Shaare Zedek Medical Center Jerusalem Israel"},{"name":"Neuropediatric Unit Department of Pediatrics Israel Multidisciplinary PraderWilli Syndrome Clinic Shaare Zedek Medical Center Jerusalem Israel"},{"name":"The Hebrew University Faculty of Medicine Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varda","family":"Gross\u2010Tsur","sequence":"additional","affiliation":[{"name":"Neuropediatric Unit Department of Pediatrics Israel Multidisciplinary PraderWilli Syndrome Clinic Shaare Zedek Medical Center Jerusalem Israel"},{"name":"The Hebrew University Faculty of Medicine Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry 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