{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:58:27Z","timestamp":1792371507081,"version":"4.4.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Multiple endocrine neoplasia type 4 (MEN4) is an autosomal dominant disorder that presents with a spectrum of clinical manifestations overlapping with those of MEN1 syndrome. It is caused by inactivating mutations of the <jats:italic>CDKN1B<\/jats:italic> gene, encoding for p27<jats:sup>kip1<\/jats:sup> cyclin-dependent kinase 2 inhibitor, implicated in cell cycle control. Eight mutations of <jats:italic>CDKN1B<\/jats:italic> in MEN4 patients have been published so far. The aim of this study was to characterize the molecular basis of a case of MEN1-like syndrome with a neuroendocrine tumor and persistent primary hyperparathyroidism (PHPT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical, biochemical, and genetic evaluation were undertaken in the proband (a 53-year-old Caucasian woman) and in one 34-year-old son. The proband was operated for recurrent PHPT. Sequence analysis of the <jats:italic>MEN1<\/jats:italic> and <jats:italic>CDKN1B<\/jats:italic> genes was performed on constitutional and parathyroid tissue DNA. Staining for p27 was carried out in parathyroid tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Neither <jats:italic>MEN1<\/jats:italic> mutations nor large deletions encompassing the <jats:italic>MEN1<\/jats:italic> gene on chromosome 11q13.1 could be detected in the proband. A germline frameshift mutation of <jats:italic>CDKN1B<\/jats:italic> (371delCT) was revealed, predicted to generate a truncated p27 (CDKN1B) protein. This mutation was confirmed on somatic DNA from the pathological parathyroid tissue, with the retention of the WT allele.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We report a germline heterozygote frameshift mutation of the <jats:italic>CDKN1B<\/jats:italic> gene in a Caucasian woman with a long clinical history of MEN1-like multiple endocrine tumors, along with the finding of the mutation in her son. This is the first report of positive <jats:italic>CDKN1B<\/jats:italic> mutation analysis in a male subject and also the first description of recurrent hyperparathyroidism in MEN4.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-14-0080","type":"journal-article","created":{"date-parts":[[2014,5,13]],"date-time":"2014-05-13T08:27:40Z","timestamp":1399969660000},"page":"K7-K17","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":49,"title":["A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome"],"prefix":"10.1093","volume":"171","author":[{"given":"Francesco","family":"Tonelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Giudici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Giusti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Marini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisella","family":"Cianferotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Nesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Brandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"5","key":"1_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; 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