Genotype–phenotype correlation in von Hippel‐Lindau disease
Background/Aims Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel‐Lindau (VHL) disease. Identification of genotype–phenotype correlation is an important prerequisite for better management, treatment and prognosis. Methods Retrospective, single‐cent...
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| Veröffentlicht in: | Acta ophthalmologica (Oxford, England) England), 2021-12, Vol.99 (8), p.e1492-e1500 |
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| creator | Reich, Michael Jaegle, Sabine Neumann‐Haefelin, Elke Klingler, Jan‐Helge Evers, Charlotte Daniel, Moritz Bucher, Felicitas Ludwig, Franziska Nuessle, Simone Kopp, Julia Boehringer, Daniel Reinhard, Thomas Lagrèze, Wolf A. Lange, Clemens Agostini, Hansjuergen Lang, Stefan J. |
| description | Background/Aims
Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel‐Lindau (VHL) disease. Identification of genotype–phenotype correlation is an important prerequisite for better management, treatment and prognosis.
Methods
Retrospective, single‐centre 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.
Results
The first clinical finding occurred at an age of 26 ± 14 years (y) [mean ± SD]. In 91 ± 3% (95% CI 88–94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age‐related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino‐acid substitution/deletion (AASD) (all p |
| doi_str_mv | 10.1111/aos.14843 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2501483819</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2501483819</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3533-786e12d47082f936b594ec013edd730523b75a7ac8c15be0ff0cd18e857854873</originalsourceid><addsrcrecordid>eNp1kEFLwzAYhoMobk4P_gEpeNFDt6RpmuwkY-gmDHZQwVtI06-Y0TW1WZXd9hME_-F-idHOHQS_y_seHl4-HoTOCe4TfwNlXZ_EIqYHqEs4YyHliTjcd_bcQSfOLTBOSJLEx6hDKY8wI0kX3UygtKt1BdvNZ_Wy64G2dQ2FWhlbBqYM3nxMTVVBsd18zEyZqSbIjAPl4BQd5apwcLbLHnq6u30cT8PZfHI_Hs1CTRmlIRcJkCiLORZRPqRJyoYxaEwoZBmnmEU05UxxpYUmLAWc51hnRIBgXLBYcNpDV-1uVdvXBtxKLo3TUBSqBNs4GTHsDVBBhh69_IMubFOX_jtPDTlNKIliT123lK6tczXksqrNUtVrSbD8tiq9Vflj1bMXu8UmXUK2J381emDQAu-mgPX_S3I0f2gnvwA-xoFX</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2597363124</pqid></control><display><type>article</type><title>Genotype–phenotype correlation in von Hippel‐Lindau disease</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Reich, Michael ; Jaegle, Sabine ; Neumann‐Haefelin, Elke ; Klingler, Jan‐Helge ; Evers, Charlotte ; Daniel, Moritz ; Bucher, Felicitas ; Ludwig, Franziska ; Nuessle, Simone ; Kopp, Julia ; Boehringer, Daniel ; Reinhard, Thomas ; Lagrèze, Wolf A. ; Lange, Clemens ; Agostini, Hansjuergen ; Lang, Stefan J.</creator><creatorcontrib>Reich, Michael ; Jaegle, Sabine ; Neumann‐Haefelin, Elke ; Klingler, Jan‐Helge ; Evers, Charlotte ; Daniel, Moritz ; Bucher, Felicitas ; Ludwig, Franziska ; Nuessle, Simone ; Kopp, Julia ; Boehringer, Daniel ; Reinhard, Thomas ; Lagrèze, Wolf A. ; Lange, Clemens ; Agostini, Hansjuergen ; Lang, Stefan J.</creatorcontrib><description>Background/Aims
Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel‐Lindau (VHL) disease. Identification of genotype–phenotype correlation is an important prerequisite for better management, treatment and prognosis.
Methods
Retrospective, single‐centre 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.
Results
The first clinical finding occurred at an age of 26 ± 14 years (y) [mean ± SD]. In 91 ± 3% (95% CI 88–94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age‐related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino‐acid substitution/deletion (AASD) (all p < 0.01), while it is reverse for PPGL (p < 0.01). Patients with a TV showed 0.10 ± 0.15 RH per y during their lifetime compared to 0.05 ± 0.07 in patients with AASD (p < 0.02). The median enucleation/phthisis‐free survival time in patients with a TV was 56y (95% CI 50–62) compared to 78y (95% CI 75–81) in patients with AASD (p < 0.02).
Conclusion
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.</description><identifier>ISSN: 1755-375X</identifier><identifier>EISSN: 1755-3768</identifier><identifier>DOI: 10.1111/aos.14843</identifier><identifier>PMID: 33720516</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adolescent ; Adult ; Age ; Aged ; Aged, 80 and over ; Central nervous system ; Child ; Clear cell-type renal cell carcinoma ; DNA Mutational Analysis ; Enucleation ; Female ; Fluorescein Angiography - methods ; Follow-Up Studies ; Fundus Oculi ; Genetic Association Studies - methods ; Genetic Predisposition to Disease ; genotype –phenotype correlation ; Genotypes ; Germany - epidemiology ; haemangioblastoma ; Hemangioblastoma - diagnosis ; Hemangioblastoma - epidemiology ; Hemangioblastoma - etiology ; Humans ; Kidney cancer ; Male ; Medical prognosis ; Middle Aged ; Morbidity - trends ; Mutation ; Neuroendocrine tumors ; Pancreatic cancer ; Pancreatic carcinoma ; Paraganglioma ; Patients ; Phenotypes ; Pheochromocytoma ; retina ; Retina - diagnostic imaging ; Retinal Neoplasms - diagnosis ; Retinal Neoplasms - epidemiology ; Retinal Neoplasms - etiology ; Retrospective Studies ; Tomography, Optical Coherence - methods ; VHL ; VHL protein ; von Hippel-Lindau Disease - complications ; von Hippel-Lindau Disease - epidemiology ; von Hippel-Lindau Disease - genetics ; Von Hippel-Lindau Tumor Suppressor Protein - genetics ; Von Hippel-Lindau Tumor Suppressor Protein - metabolism ; von Hippel‐Lindau disease ; Young Adult</subject><ispartof>Acta ophthalmologica (Oxford, England), 2021-12, Vol.99 (8), p.e1492-e1500</ispartof><rights>2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Foundation.</rights><rights>2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3533-786e12d47082f936b594ec013edd730523b75a7ac8c15be0ff0cd18e857854873</citedby><cites>FETCH-LOGICAL-c3533-786e12d47082f936b594ec013edd730523b75a7ac8c15be0ff0cd18e857854873</cites><orcidid>0000-0002-5324-7002 ; 0000-0002-3558-5905 ; 0000-0003-4401-8344</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Faos.14843$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Faos.14843$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,1427,27903,27904,45553,45554,46387,46811</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33720516$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reich, Michael</creatorcontrib><creatorcontrib>Jaegle, Sabine</creatorcontrib><creatorcontrib>Neumann‐Haefelin, Elke</creatorcontrib><creatorcontrib>Klingler, Jan‐Helge</creatorcontrib><creatorcontrib>Evers, Charlotte</creatorcontrib><creatorcontrib>Daniel, Moritz</creatorcontrib><creatorcontrib>Bucher, Felicitas</creatorcontrib><creatorcontrib>Ludwig, Franziska</creatorcontrib><creatorcontrib>Nuessle, Simone</creatorcontrib><creatorcontrib>Kopp, Julia</creatorcontrib><creatorcontrib>Boehringer, Daniel</creatorcontrib><creatorcontrib>Reinhard, Thomas</creatorcontrib><creatorcontrib>Lagrèze, Wolf A.</creatorcontrib><creatorcontrib>Lange, Clemens</creatorcontrib><creatorcontrib>Agostini, Hansjuergen</creatorcontrib><creatorcontrib>Lang, Stefan J.</creatorcontrib><title>Genotype–phenotype correlation in von Hippel‐Lindau disease</title><title>Acta ophthalmologica (Oxford, England)</title><addtitle>Acta Ophthalmol</addtitle><description>Background/Aims
Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel‐Lindau (VHL) disease. Identification of genotype–phenotype correlation is an important prerequisite for better management, treatment and prognosis.
Methods
Retrospective, single‐centre 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.
Results
The first clinical finding occurred at an age of 26 ± 14 years (y) [mean ± SD]. In 91 ± 3% (95% CI 88–94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age‐related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino‐acid substitution/deletion (AASD) (all p < 0.01), while it is reverse for PPGL (p < 0.01). Patients with a TV showed 0.10 ± 0.15 RH per y during their lifetime compared to 0.05 ± 0.07 in patients with AASD (p < 0.02). The median enucleation/phthisis‐free survival time in patients with a TV was 56y (95% CI 50–62) compared to 78y (95% CI 75–81) in patients with AASD (p < 0.02).
Conclusion
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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Central nervous system</subject><subject>Child</subject><subject>Clear cell-type renal cell carcinoma</subject><subject>DNA Mutational Analysis</subject><subject>Enucleation</subject><subject>Female</subject><subject>Fluorescein Angiography - methods</subject><subject>Follow-Up Studies</subject><subject>Fundus Oculi</subject><subject>Genetic Association Studies - methods</subject><subject>Genetic Predisposition to Disease</subject><subject>genotype –phenotype correlation</subject><subject>Genotypes</subject><subject>Germany - epidemiology</subject><subject>haemangioblastoma</subject><subject>Hemangioblastoma - diagnosis</subject><subject>Hemangioblastoma - epidemiology</subject><subject>Hemangioblastoma - etiology</subject><subject>Humans</subject><subject>Kidney cancer</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Morbidity - trends</subject><subject>Mutation</subject><subject>Neuroendocrine tumors</subject><subject>Pancreatic cancer</subject><subject>Pancreatic carcinoma</subject><subject>Paraganglioma</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Pheochromocytoma</subject><subject>retina</subject><subject>Retina - diagnostic imaging</subject><subject>Retinal Neoplasms - diagnosis</subject><subject>Retinal Neoplasms - epidemiology</subject><subject>Retinal Neoplasms - etiology</subject><subject>Retrospective Studies</subject><subject>Tomography, Optical Coherence - methods</subject><subject>VHL</subject><subject>VHL protein</subject><subject>von Hippel-Lindau Disease - complications</subject><subject>von Hippel-Lindau Disease - epidemiology</subject><subject>von Hippel-Lindau Disease - genetics</subject><subject>Von Hippel-Lindau Tumor Suppressor Protein - genetics</subject><subject>Von Hippel-Lindau Tumor Suppressor Protein - metabolism</subject><subject>von Hippel‐Lindau disease</subject><subject>Young Adult</subject><issn>1755-375X</issn><issn>1755-3768</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kEFLwzAYhoMobk4P_gEpeNFDt6RpmuwkY-gmDHZQwVtI06-Y0TW1WZXd9hME_-F-idHOHQS_y_seHl4-HoTOCe4TfwNlXZ_EIqYHqEs4YyHliTjcd_bcQSfOLTBOSJLEx6hDKY8wI0kX3UygtKt1BdvNZ_Wy64G2dQ2FWhlbBqYM3nxMTVVBsd18zEyZqSbIjAPl4BQd5apwcLbLHnq6u30cT8PZfHI_Hs1CTRmlIRcJkCiLORZRPqRJyoYxaEwoZBmnmEU05UxxpYUmLAWc51hnRIBgXLBYcNpDV-1uVdvXBtxKLo3TUBSqBNs4GTHsDVBBhh69_IMubFOX_jtPDTlNKIliT123lK6tczXksqrNUtVrSbD8tiq9Vflj1bMXu8UmXUK2J381emDQAu-mgPX_S3I0f2gnvwA-xoFX</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>Reich, Michael</creator><creator>Jaegle, Sabine</creator><creator>Neumann‐Haefelin, Elke</creator><creator>Klingler, Jan‐Helge</creator><creator>Evers, Charlotte</creator><creator>Daniel, Moritz</creator><creator>Bucher, Felicitas</creator><creator>Ludwig, Franziska</creator><creator>Nuessle, Simone</creator><creator>Kopp, Julia</creator><creator>Boehringer, Daniel</creator><creator>Reinhard, Thomas</creator><creator>Lagrèze, Wolf A.</creator><creator>Lange, Clemens</creator><creator>Agostini, Hansjuergen</creator><creator>Lang, Stefan J.</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5324-7002</orcidid><orcidid>https://orcid.org/0000-0002-3558-5905</orcidid><orcidid>https://orcid.org/0000-0003-4401-8344</orcidid></search><sort><creationdate>202112</creationdate><title>Genotype–phenotype correlation in von Hippel‐Lindau disease</title><author>Reich, Michael ; Jaegle, Sabine ; Neumann‐Haefelin, Elke ; Klingler, Jan‐Helge ; Evers, Charlotte ; Daniel, Moritz ; Bucher, Felicitas ; Ludwig, Franziska ; Nuessle, Simone ; Kopp, Julia ; Boehringer, Daniel ; Reinhard, Thomas ; Lagrèze, Wolf A. ; Lange, Clemens ; Agostini, Hansjuergen ; Lang, Stefan J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3533-786e12d47082f936b594ec013edd730523b75a7ac8c15be0ff0cd18e857854873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Central nervous system</topic><topic>Child</topic><topic>Clear cell-type renal cell carcinoma</topic><topic>DNA Mutational Analysis</topic><topic>Enucleation</topic><topic>Female</topic><topic>Fluorescein Angiography - methods</topic><topic>Follow-Up Studies</topic><topic>Fundus Oculi</topic><topic>Genetic Association Studies - methods</topic><topic>Genetic Predisposition to Disease</topic><topic>genotype –phenotype correlation</topic><topic>Genotypes</topic><topic>Germany - epidemiology</topic><topic>haemangioblastoma</topic><topic>Hemangioblastoma - diagnosis</topic><topic>Hemangioblastoma - epidemiology</topic><topic>Hemangioblastoma - etiology</topic><topic>Humans</topic><topic>Kidney cancer</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Morbidity - trends</topic><topic>Mutation</topic><topic>Neuroendocrine tumors</topic><topic>Pancreatic cancer</topic><topic>Pancreatic carcinoma</topic><topic>Paraganglioma</topic><topic>Patients</topic><topic>Phenotypes</topic><topic>Pheochromocytoma</topic><topic>retina</topic><topic>Retina - diagnostic imaging</topic><topic>Retinal Neoplasms - diagnosis</topic><topic>Retinal Neoplasms - epidemiology</topic><topic>Retinal Neoplasms - etiology</topic><topic>Retrospective Studies</topic><topic>Tomography, Optical Coherence - methods</topic><topic>VHL</topic><topic>VHL protein</topic><topic>von Hippel-Lindau Disease - complications</topic><topic>von Hippel-Lindau Disease - epidemiology</topic><topic>von Hippel-Lindau Disease - genetics</topic><topic>Von Hippel-Lindau Tumor Suppressor Protein - genetics</topic><topic>Von Hippel-Lindau Tumor Suppressor Protein - metabolism</topic><topic>von Hippel‐Lindau disease</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reich, Michael</creatorcontrib><creatorcontrib>Jaegle, Sabine</creatorcontrib><creatorcontrib>Neumann‐Haefelin, Elke</creatorcontrib><creatorcontrib>Klingler, Jan‐Helge</creatorcontrib><creatorcontrib>Evers, Charlotte</creatorcontrib><creatorcontrib>Daniel, Moritz</creatorcontrib><creatorcontrib>Bucher, Felicitas</creatorcontrib><creatorcontrib>Ludwig, Franziska</creatorcontrib><creatorcontrib>Nuessle, Simone</creatorcontrib><creatorcontrib>Kopp, Julia</creatorcontrib><creatorcontrib>Boehringer, Daniel</creatorcontrib><creatorcontrib>Reinhard, Thomas</creatorcontrib><creatorcontrib>Lagrèze, Wolf A.</creatorcontrib><creatorcontrib>Lange, Clemens</creatorcontrib><creatorcontrib>Agostini, Hansjuergen</creatorcontrib><creatorcontrib>Lang, Stefan J.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta ophthalmologica (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reich, Michael</au><au>Jaegle, Sabine</au><au>Neumann‐Haefelin, Elke</au><au>Klingler, Jan‐Helge</au><au>Evers, Charlotte</au><au>Daniel, Moritz</au><au>Bucher, Felicitas</au><au>Ludwig, Franziska</au><au>Nuessle, Simone</au><au>Kopp, Julia</au><au>Boehringer, Daniel</au><au>Reinhard, Thomas</au><au>Lagrèze, Wolf A.</au><au>Lange, Clemens</au><au>Agostini, Hansjuergen</au><au>Lang, Stefan J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genotype–phenotype correlation in von Hippel‐Lindau disease</atitle><jtitle>Acta ophthalmologica (Oxford, England)</jtitle><addtitle>Acta Ophthalmol</addtitle><date>2021-12</date><risdate>2021</risdate><volume>99</volume><issue>8</issue><spage>e1492</spage><epage>e1500</epage><pages>e1492-e1500</pages><issn>1755-375X</issn><eissn>1755-3768</eissn><abstract>Background/Aims
Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel‐Lindau (VHL) disease. Identification of genotype–phenotype correlation is an important prerequisite for better management, treatment and prognosis.
Methods
Retrospective, single‐centre 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.
Results
The first clinical finding occurred at an age of 26 ± 14 years (y) [mean ± SD]. In 91 ± 3% (95% CI 88–94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age‐related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino‐acid substitution/deletion (AASD) (all p < 0.01), while it is reverse for PPGL (p < 0.01). Patients with a TV showed 0.10 ± 0.15 RH per y during their lifetime compared to 0.05 ± 0.07 in patients with AASD (p < 0.02). The median enucleation/phthisis‐free survival time in patients with a TV was 56y (95% CI 50–62) compared to 78y (95% CI 75–81) in patients with AASD (p < 0.02).
Conclusion
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.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33720516</pmid><doi>10.1111/aos.14843</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-5324-7002</orcidid><orcidid>https://orcid.org/0000-0002-3558-5905</orcidid><orcidid>https://orcid.org/0000-0003-4401-8344</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Age Aged Aged, 80 and over Central nervous system Child Clear cell-type renal cell carcinoma DNA Mutational Analysis Enucleation Female Fluorescein Angiography - methods Follow-Up Studies Fundus Oculi Genetic Association Studies - methods Genetic Predisposition to Disease genotype –phenotype correlation Genotypes Germany - epidemiology haemangioblastoma Hemangioblastoma - diagnosis Hemangioblastoma - epidemiology Hemangioblastoma - etiology Humans Kidney cancer Male Medical prognosis Middle Aged Morbidity - trends Mutation Neuroendocrine tumors Pancreatic cancer Pancreatic carcinoma Paraganglioma Patients Phenotypes Pheochromocytoma retina Retina - diagnostic imaging Retinal Neoplasms - diagnosis Retinal Neoplasms - epidemiology Retinal Neoplasms - etiology Retrospective Studies Tomography, Optical Coherence - methods VHL VHL protein von Hippel-Lindau Disease - complications von Hippel-Lindau Disease - epidemiology von Hippel-Lindau Disease - genetics Von Hippel-Lindau Tumor Suppressor Protein - genetics Von Hippel-Lindau Tumor Suppressor Protein - metabolism von Hippel‐Lindau disease Young Adult |
| title | Genotype–phenotype correlation in von Hippel‐Lindau disease |
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