{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:07:12Z","timestamp":1789589232397,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background\/Aims<\/jats:title>\n                    <jats:p>Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel\u2010Lindau (VHL) disease. Identification of genotype\u2013phenotype correlation is an important prerequisite for better management, treatment and prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective, single\u2010centre cohort study of 200 VHL patients. Genetic data and date of onset of RH, central nervous system haemangioblastomas (CNSH), pheochromocytoma\/paraganglioma (PPGL), clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine neoplasm (PNEN) were collected. The number and locations of RH were recorded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The first clinical finding occurred at an age of 26\u2009\u00b1\u200914\u2009years (y) [mean\u2009\u00b1\u2009SD]. In 91\u2009\u00b1\u20093% (95% CI 88\u201394) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare\n                      <jats:italic>VHL<\/jats:italic>\n                      gene variants in 166 patients were detected. A higher age\u2010related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino\u2010acid substitution\/deletion (AASD) (all p\u2009&lt;\u20090.01), while it is reverse for PPGL (p\u2009&lt;\u20090.01). Patients with a TV showed 0.10\u2009\u00b1\u20090.15 RH per y during their lifetime compared to 0.05\u2009\u00b1\u20090.07 in patients with AASD (p\u2009&lt;\u20090.02). The median enucleation\/phthisis\u2010free survival time in patients with a TV was 56y (95% CI 50\u201362) compared to 78y (95% CI 75\u201381) in patients with AASD (p\u2009&lt;\u20090.02).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Compared to patients with AASD, patients with a TV develop RH, CNSH, ccRCC and PNEN earlier. They experience a higher number of RH and bear a higher risk of enucleation\/phthisis. Thus, patients with a TV might be considered for a more intensive ophthalmological monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aos.14843","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T06:43:32Z","timestamp":1615790612000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Genotype\u2013phenotype correlation in von Hippel\u2010Lindau disease"],"prefix":"10.1111","volume":"99","author":[{"given":"Michael","family":"Reich","sequence":"first","affiliation":[{"name":"Eye Centre Medical Centre \u2010 University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Jaegle","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Medical Centre \u2010 University of Freiburg Faculty of Medicine University of Freiburg Freiburg 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