{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:45:22Z","timestamp":1789595122802,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,8,12]],"date-time":"2008-08-12T00:00:00Z","timestamp":1218499200000},"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":[[2009,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> Homozygous mutations in the gene encoding the pituitary transcription factor PROP1 are associated with combined pituitary hormone deficiency (CPHD) in both mice and humans with a highly variable phenotype with respect to the severity and time of initiation of pituitary hormone deficiency. We have ascertained three pedigrees with <jats:italic>PROP1<\/jats:italic> mutations from a large cohort of patients with variable degrees of CPHD who were screened for mutations in <jats:italic>PROP1<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Affected individuals from all three pedigrees were found to harbour novel <jats:italic>PROP1<\/jats:italic> mutations. We have identified two siblings in one family who were homozygous for an intronic mutation (c.343\u201311C\u00a0&gt;\u00a0G) that disrupts correct splicing resulting in the loss of exon 3 from the <jats:italic>PROP1<\/jats:italic> transcript. Two siblings from a second, unrelated family are compound heterozygotes for two point mutations in the coding region, a missense mutation (p.R125W) that leads to impaired transcriptional activation, and a deletion of a single nucleotide (c.310delC) resulting in a frameshift and nonfunctional mutant protein. Additionally, we identified a homozygous deletion of the <jats:italic>PROP1<\/jats:italic> locus in two patients born to consanguineous parents.<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> Mutations in <jats:italic>PROP1<\/jats:italic> are a frequent cause of familial CPHD. We have described four novel mutations in <jats:italic>PROP1<\/jats:italic> in 3 pedigrees, all resulting in PROP1 deficiency by different mechanisms. The phenotypic variation observed in association with <jats:italic>PROP1<\/jats:italic> mutations both within and between families, together with the evolving nature of hormone deficiencies and sometimes changing pituitary morphology indicates a need for continual monitoring of these patients.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2008.03326.x","type":"journal-article","created":{"date-parts":[[2008,8,12]],"date-time":"2008-08-12T08:27:19Z","timestamp":1218529639000},"page":"96-103","source":"Crossref","is-referenced-by-count":40,"title":["Molecular analysis of novel <i>PROP1<\/i> mutations associated with combined pituitary hormone deficiency (CPHD)"],"prefix":"10.1111","volume":"70","author":[{"given":"D.","family":"Kelberman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P. G.","family":"Turton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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