{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:12:24Z","timestamp":1791353544174,"version":"4.3.1"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T00:00:00Z","timestamp":1438819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Combined pituitary hormonal deficiency (\n                      <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content>\n                      ) can result from mutations within genes that encode transcription factors. This study evaluated the frequency of mutations in these genes in a cohort of 144 unrelated Italian patients with\n                      <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content>\n                      and estimated the overall prevalence of mutations across different populations using a systematic literature review.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and methods<\/jats:title>\n                    <jats:p>\n                      A multicentre study of adult and paediatric patients with\n                      <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content>\n                      was performed. The\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">PROP<\/jats:styled-content>\n                        1,\n                        <jats:styled-content style=\"fixed-case\">POU<\/jats:styled-content>\n                        1F1,\n                        <jats:styled-content style=\"fixed-case\">HESX<\/jats:styled-content>\n                        1,\n                        <jats:styled-content style=\"fixed-case\">LHX<\/jats:styled-content>\n                        3\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">LHX<\/jats:styled-content>\n                        4\n                      <\/jats:italic>\n                      genes were analysed for the presence of mutations using direct sequencing. We systematically searched PubMed with no date restrictions for studies that reported genetic screening of\n                      <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content>\n                      cohorts. We only considered genetic screenings with at least 10 individuals. Data extraction was conducted in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses (\n                      <jats:styled-content style=\"fixed-case\">PRISMA<\/jats:styled-content>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Global mutation frequency in Italian patients with\n                      <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content>\n                      was 2\u00b79% (4\/136) in sporadic cases and 12\u00b75% (1\/8) in familial cases. The worldwide mutation frequency for the five genes calculated from 21 studies was 12\u00b74%, which ranged from 11\u00b72% in sporadic to 63% in familial cases.\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">PROP<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      was the most frequently mutated gene in sporadic (6\u00b77%) and familial cases (48\u00b75%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The frequency of defects in genes encoding pituitary transcription factors is quite low in Italian patients with\n                      <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content>\n                      and other western European countries, especially in sporadic patients. The decision of which genes should be tested and in which order should be guided by hormonal and imaging phenotype, the presence of extrapituitary abnormalities and the frequency of mutation for each gene in the patient\u2010referring population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.12849","type":"journal-article","created":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T08:23:51Z","timestamp":1436171031000},"page":"849-860","source":"Crossref","is-referenced-by-count":65,"title":["Frequency of genetic defects in combined pituitary hormone deficiency: a systematic review and analysis of a multicentre Italian cohort"],"prefix":"10.1111","volume":"83","author":[{"given":"Francesca","family":"De Rienzo","sequence":"first","affiliation":[{"name":"Unit of Paediatrics Department of Health Sciences University of Eastern Piedmont Novara 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