{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:24:28Z","timestamp":1791170668371,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The aim of this study was to investigate the presence of germline mutations in the\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      gene that encodes the cyclin-dependent kinase (Cdk) inhibitor p27 in multiple endocrine neoplasia 1 (MEN1)-like Spanish index patients. The\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      gene has recently been identified as a tumor susceptibility gene for MEN4, with six germline mutations reported so far in patients with a MEN-like phenotype but negative for MEN1 mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and methods<\/jats:title>\n                    <jats:p>\n                      Fifteen Spanish index cases with MEN-like symptoms were screened for mutations in the\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      gene and the mutant variant was studied functionally by transcription\/translation assays\n                      <jats:italic>in vitro<\/jats:italic>\n                      and in transiently transfected HeLa cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We report the identification of a heterozygous GAGA deletion in the 5\u2032-UTR of\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      , NM_004064.3:c.-32_-29del, in a patient affected by gastric carcinoid tumor and hyperparathyroidism. This deletion falls inside the region that is responsible for\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      transcription and is predicted to destroy a secondary stem and loop structure that includes the GAGAGA element responsible for ribosome recruitment. Accordingly,\n                      <jats:italic>in vitro<\/jats:italic>\n                      studies of coupled transcription\/translation assays and transient transfection in HeLa cells showed that the GAGA deletion in the\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      5\u2032-UTR significantly impairs the transcription of downstream reporter luciferase (of \u223c40\u201360%) and, possibly, the translation of the corresponding mRNA. This mutation was associated with a significant reduction in the amount of\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      mRNA in peripheral blood leukocytes from the patient, as demonstrated by quantitative real-time PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our results confirm that germline\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      mutations may predispose to a human MEN4 condition and add novel evidence that alteration in the transcription\/translation rate of\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      mRNA might be the mechanism implicated in tumor susceptibility.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eje-11-0929","type":"journal-article","created":{"date-parts":[[2011,12,2]],"date-time":"2011-12-02T04:25:00Z","timestamp":1322799900000},"page":"551-560","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":61,"title":["Functional characterization of a rare germline mutation in the gene encoding the cyclin-dependent kinase inhibitor p27Kip1 (CDKN1B) in a Spanish patient with multiple endocrine neoplasia-like phenotype"],"prefix":"10.1093","volume":"166","author":[{"given":"Donatella","family":"Malanga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"De Gisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Riccardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Scrima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"De Marco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Robledo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Viglietto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"1_41979633","first-page":"15558","volume":"17","year":"2006","journal-title":"PNAS","ISSN":"https:\/\/id.crossref.org\/issn\/0027-8424","issn-type":"print"},{"issue":"8","key":"2_28745916","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.1210\/jc.2006-2843","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"5","key":"3_33426288","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1210\/jc.2008-2083","volume":"94","year":"2009","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"11","key":"4_38098752","doi-asserted-by":"publisher","first-page":"E1825","DOI":"10.1002\/humu.21354","volume":"31","author":"Molatore","year":"2010","journal-title":"Human mutation","ISSN":"https:\/\/id.crossref.org\/issn\/1059-7794","issn-type":"print"},{"issue":"1","key":"5_38458622","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1159\/000320366","volume":"93","author":"Marinoni","year":"2011","journal-title":"Neuroendocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0028-3835","issn-type":"print"},{"issue":"1","key":"6_6494013","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/(SICI)1097-4652(200004)183:1<10::AID-JCP2>3.0.CO;2-I","volume":"183","author":"Slingerland","year":"2000","journal-title":"Journal of cellular physiology","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9541","issn-type":"print"},{"issue":"4","key":"7_30689447","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nrc2347","volume":"8","author":"Chu","year":"2008","journal-title":"Nature reviews. 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