{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:32:55Z","timestamp":1790137975445,"version":"4.0.1"},"reference-count":47,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Mutations in\n                      <jats:italic>PTPN11<\/jats:italic>\n                      are associated with Noonan syndrome (NS). Although the effectiveness of growth hormone therapy (GHT) in treating short stature due to NS has been previously demonstrated, the effect of\n                      <jats:italic>PTPN11<\/jats:italic>\n                      mutation status on the long-term outcomes of GHT remains to be elucidated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This analysis included pooled data from the observational American Norditropin Studies: Web-Enabled Research Program (NCT01009905) and the randomized, double-blinded GHLIQUID-4020 clinical trial (NCT01927861). Pediatric patients with clinically diagnosed NS and confirmed\n                      <jats:italic>PTPN11<\/jats:italic>\n                      mutation status were eligible for inclusion. The effectiveness analysis included patients who were GHT-na\u00efve and pre-pubertal at GHT start. Growth outcomes and safety were assessed over 4 years of GHT (Norditropin\u00ae, Novo Nordisk A\/S).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 69 patients were included in the effectiveness analysis (71%\n                      <jats:italic>PTPN11<\/jats:italic>\n                      positive). The proportion of females was 32.7 and 30.0% in\n                      <jats:italic>PTPN11<\/jats:italic>\n                      -positive and negative patients, respectively, and mean age at GHT start was 6.4 years in both groups. Using general population reference data, after 4 years of GHT, the mean (\n                      <jats:sc>s.d.<\/jats:sc>\n                      ) height SD score (HSDS) was \u22121.9 (1.1) and \u22121.7 (0.8) for\n                      <jats:italic>PTPN11<\/jats:italic>\n                      -positive and\n                      <jats:italic>PTPN11<\/jats:italic>\n                      -negative patients, respectively, with no statistical difference observed between groups. The mean (\n                      <jats:sc>s.d.<\/jats:sc>\n                      ) change in HSDS at 4 years was +1.3 (0.8) in\n                      <jats:italic>PTPN11<\/jats:italic>\n                      -positive patients and +1.5 (0.7) in\n                      <jats:italic>PTPN11-<\/jats:italic>\n                      negative patients (no significant differences between groups). Safety findings were consistent with previous analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      GHT resulted in improved growth outcomes over 4 years in GHT-na\u00efve, pre-pubertal NS patients, irrespective of\n                      <jats:italic>PTPN11<\/jats:italic>\n                      mutation status.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-21-0615","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T12:01:23Z","timestamp":1646395283000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":13,"title":["Outcomes in growth hormone-treated Noonan syndrome children: impact of PTPN11 mutation status"],"prefix":"10.1530","volume":"11","author":[{"given":"Alexander A L","family":"Jorge","sequence":"first","affiliation":[{"name":"Unidade de Endocrinologia-Genetica, LIM\/25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Edouard","sequence":"additional","affiliation":[{"name":"Endocrine, Bone Diseases, and Genetics Unit, Children\u2019s Hospital, Toulouse University Hospital, RESTORE INSERM UMR1301, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Maghnie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy"},{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Pietropoli","sequence":"additional","affiliation":[{"name":"Novo Nordisk Health Care AG, Global Medical Affairs Biopharm, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicky","family":"Kelepouris","sequence":"additional","affiliation":[{"name":"Novo Nordisk Inc., Clinical, Medical and Regulatory Biopharm-RED, Plainsboro, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, New York Medical College, Valhalla, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Zenker","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics & Department of Pediatrics, University Hospital, Otto-von-Guericke University Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Horikawa","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolism, National Center for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"American Journal of Medical Genetics: Part A","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1002\/ajmg.a.20502","article-title":"Adult height in Noonan syndrome","volume":"123A","author":"Noonan","year":"2003","unstructured":"Noonan JARaaijmakers RHall BD. 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