{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T04:45:38Z","timestamp":1771303538264,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,2,7]],"date-time":"2012-02-07T00:00:00Z","timestamp":1328572800000},"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":[[2012,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background\u2002<\/jats:bold> Mutations in the <jats:italic>POU1F1<\/jats:italic> gene severely affect the development and function of the anterior pituitary gland and lead to combined pituitary hormone deficiency (CPHD).<\/jats:p><jats:p><jats:bold>Objective\u2002<\/jats:bold> The clinical and genetic analysis of a patient presenting with CPHD and functional characterization of identified mutations.<\/jats:p><jats:p><jats:bold>Patient\u2002<\/jats:bold> We describe a male patient with extreme short stature, learning difficulties, anterior pituitary hypoplasia, secondary hypothyroidism and undetectable prolactin, growth hormone (GH) and insulin\u2010like growth factor 1 (IGF1), with normal random cortisol.<\/jats:p><jats:p><jats:bold>Design\u2002<\/jats:bold> The <jats:italic>POU1F1<\/jats:italic> coding region was amplified by PCR and sequenced; the functional consequence of the mutations was analysed by cell transfection and <jats:italic>in vitro<\/jats:italic> assays.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Genetic analysis revealed compound heterozygosity for two novel putative loss of function mutations in <jats:italic>POU1F1<\/jats:italic>: a transition at position +3 of intron 1 [IVS1+3nt(A&gt;G)] and a point mutation in exon 6 resulting in a substitution of arginine by tryptophan (R265W). Functional analysis revealed that IVS1+3nt(A&gt;G) results in a reduction in the correctly spliced <jats:italic>POU1F1<\/jats:italic> mRNA, which could be corrected by mutations of the +4, +5 and +6 nucleotides. Analysis of POU1F1<jats:sup>R265W<\/jats:sup> revealed complete loss of function resulting from severely reduced protein stability.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> Combined pituitary hormone deficiency in this patient is caused by loss of POU1F1 function by two novel mechanisms, namely aberrant splicing (IVS1+3nt (A&gt;G) and protein instability (R265W). Identification of the genetic basis of CPHD enabled the cessation of hydrocortisone therapy without the need for further assessment for evolving endocrinopathy.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2011.04236.x","type":"journal-article","created":{"date-parts":[[2011,10,19]],"date-time":"2011-10-19T16:03:38Z","timestamp":1319040218000},"page":"387-393","source":"Crossref","is-referenced-by-count":17,"title":["Two novel mutations in the <i>POU1F1<\/i> gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency"],"prefix":"10.1111","volume":"76","author":[{"given":"J.P.","family":"Turton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Strom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Langham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.T.","family":"Dattani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Le Tissier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,2,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/344661"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/477"},{"key":"e_1_2_6_4_2","first-page":"2442","article-title":"Mutations within Sox2\/SOX2 are 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