{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:12:21Z","timestamp":1791353541180,"version":"4.3.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T00:00:00Z","timestamp":1153180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> Mutations of the <jats:italic>PROP1<\/jats:italic> gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH\/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD.<\/jats:p><jats:p><jats:bold>Design, patients and measurements\u2002<\/jats:bold> A multicentric study involving 46 cases of CPHD (17 familial cases belonging to seven kindreds and 29 sporadic cases) selected on the basis of clinical and hormonal evidence of GH deficiency, central hypothyroidism and hypogonadotrophic hypogonadism, in the absence of an identified cause of hypopituitarism. Mutations of <jats:italic>PROP1<\/jats:italic> were investigated by DNA sequencing. Clinical, hormonal and neuroradiological data were collected at each centre.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold>  <jats:italic>PROP1<\/jats:italic> mutations were identified in all familial cases: five kindreds presented a <jats:italic>c.<\/jats:italic> 301\u2013302delAG mutation, one kindred presented a <jats:italic>c.<\/jats:italic> 358C\u00a0\u2192\u00a0T (R120C) mutation and one presented a previously unreported initiation codon mutation, <jats:italic>c.<\/jats:italic> 2T\u00a0\u2192\u00a0C. Of the 29 sporadic cases, only two (6\u00b79%) presented <jats:italic>PROP1<\/jats:italic> germline mutations (<jats:italic>c.<\/jats:italic> 301\u2013302delAG, in both). Phenotypic variability was observed among patients with the same mutations, particularly the presence and age of onset of hypocortisolism, the levels of PRL and the results of pituitary imaging. One patient presented a sellar mass that persisted into adulthood.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> This is the first report of a mutation in the initiation codon of the <jats:italic>PROP1<\/jats:italic> gene and this further expands the spectrum of known mutations responsible for CPHD. The low mutation frequency observed in sporadic cases may be due to the involvement of other unidentified acquired or genetic causes.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2006.02617.x","type":"journal-article","created":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T20:13:03Z","timestamp":1153253583000},"page":"479-485","source":"Crossref","is-referenced-by-count":34,"title":["<i>PROP1<\/i> gene analysis in Portuguese patients with combined pituitary hormone deficiency"],"prefix":"10.1111","volume":"65","author":[{"given":"Manuel 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