{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:09:50Z","timestamp":1783548590762,"version":"3.55.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004257","name":"Western Norway Regional Health Authority","doi-asserted-by":"publisher","award":["911977"],"award-info":[{"award-number":["911977"]}],"id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004257","name":"Western Norway Regional Health Authority","doi-asserted-by":"publisher","award":["912161"],"award-info":[{"award-number":["912161"]}],"id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004257","name":"Western Norway Regional Health Authority","doi-asserted-by":"publisher","award":["911746"],"award-info":[{"award-number":["911746"]}],"id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dr Jon S. Larsens Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ocular pterygium-digital keloid dysplasia (OPDKD) presents in childhood with ingrowth of vascularized connective tissue on the cornea leading to severely reduced vision. Later the patients develop keloids on digits but are otherwise healthy. The overgrowth in OPDKD affects body parts that typically have lower temperature than 37\u00b0C. We present evidence that OPDKD is associated with a temperature sensitive, activating substitution, p.(Asn666Tyr), in PDGFRB. Phosphorylation levels of PDGFRB and downstream targets were higher in OPDKD fibroblasts at 37\u00b0C but were further greatly increased at the average corneal temperature of 32\u00b0C. This suggests that the substitution cause significant constitutive autoactivation mainly at lower temperature.<\/jats:p>\n               <jats:p>In contrast, a different substitution in the same codon, p.(Asn666Ser), is associated with Penttinen type of premature aging syndrome. This devastating condition is characterized by widespread tissue degeneration, including pronounced chronic ulcers and osteolytic resorption in distal limbs. In Penttinen syndrome fibroblasts, equal and high levels of phosphorylated PDGFRB was present at both 32\u00b0C and 37\u00b0C. This indicates that this substitution causes severe constitutive autoactivation of PDGFRB regardless of temperature. In line with this, most downstream targets were not affected by lower temperature. However, STAT1, important for tissue wasting, did show further increased phosphorylation at 32\u00b0C. Temperature-dependent autoactivation offers an explanation to the strikingly different clinical outcomes of substitutions in the Asn666 codon of PDGFRB.<\/jats:p>","DOI":"10.1093\/hmg\/ddab014","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T13:45:31Z","timestamp":1610631931000},"page":"72-77","source":"Crossref","is-referenced-by-count":14,"title":["Temperature-dependent autoactivation associated with clinical variability of <i>PDGFRB<\/i> Asn666 substitutions"],"prefix":"10.1093","volume":"30","author":[{"given":"Cecilie","family":"Bredrup","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Haukeland University Hospital, Bergen 5021, Norway"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen 5020, Norway"},{"name":"Department of Medical Genetics, Haukeland University Hospital, Bergen 5021, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana","family":"Cristea","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Bergen, Bergen 5020, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen Abu","family":"Safieh","sequence":"additional","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Kingdom of Saudi Arabia"},{"name":"Genomics Research Department, Research Center, King Fahad Medical City, Riyadh 11564, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Di Maria","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Genova, Genova 16132, Italy"},{"name":"Unit of Medical Genetics, Galliera Hospital, Genova 16128, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn Tore","family":"Gjertsen","sequence":"additional","affiliation":[{"name":"Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen 5021, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e5re Steinar","family":"Tveit","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Haukeland University Hospital, Bergen 5021, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frode","family":"Thu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Oslo University Hospital, Oslo 4956, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Bull","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Haukeland University Hospital, Bergen 5021, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak P","family":"Edward","sequence":"additional","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Kingdom of Saudi Arabia"},{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul C M","family":"Hennekam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 1105AZ, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"H\u00f8vding","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Haukeland University Hospital, Bergen 5021, Norway"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen 5020, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olav H","family":"Haugen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Haukeland University Hospital, Bergen 5021, Norway"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen 5020, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Houge","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Haukeland University Hospital, Bergen 5021, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyvind","family":"R\u00f8dahl","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Haukeland University Hospital, Bergen 5021, Norway"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen 5020, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ove","family":"Bruland","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Haukeland University Hospital, Bergen 5021, 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