{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:45:01Z","timestamp":1790952301296,"version":"4.1.0"},"reference-count":185,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CONAHCYT, \u201cCiencia B\u00e1sica, Ciencia de Frontera Modalidad: Paradigmas y Controversias de la Ciencia 2022\u201d","award":["319578"],"award-info":[{"award-number":["319578"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>This review article focuses on von Hippel\u2013Lindau (VHL) disease, a rare genetic disorder characterized by the development of tumors and cysts throughout the body. It discusses the following aspects of the disease. Genetics: VHL disease is caused by mutations in the VHL tumor suppressor gene located on chromosome 3. These mutations can be inherited or occur spontaneously. This article details the different types of mutations and their associated clinical features. Pathophysiology: The underlying cause of VHL disease is the loss of function of the VHL protein (pVHL). This protein normally regulates hypoxia-inducible factors (HIFs), which are involved in cell growth and survival. When pVHL is dysfunctional, HIF levels become elevated, leading to uncontrolled cell growth and tumor formation. Clinical Manifestations: VHL disease can affect various organs, including the brain, spinal cord, retina, kidneys, pancreas, and adrenal glands. Symptoms depend on the location and size of the tumors. Diagnosis: Diagnosis of VHL disease involves a combination of clinical criteria, imaging studies, and genetic testing. Treatment: Treatment options for VHL disease depend on the type and location of the tumors. Surgery is the mainstay of treatment, but other options like radiation therapy may also be used. Challenges: This article highlights the challenges in VHL disease management, including the lack of effective therapies for some tumor types and the need for better methods to monitor disease progression. In conclusion, we emphasize the importance of ongoing research to develop new and improved treatments for VHL disease.<\/jats:p>","DOI":"10.3390\/diagnostics14171909","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T11:12:13Z","timestamp":1724929933000},"page":"1909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genetics, Pathophysiology, and Current Challenges in Von Hippel\u2013Lindau Disease Therapeutics"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7765-8159","authenticated-orcid":false,"given":"Laura","family":"G\u00f3mez-Virgilio","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Reprogramming, Department of Physiology, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad No. 3000, Coyoacan CDMX 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireya","family":"Velazquez-Paniagua","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Reprogramming, Department of Physiology, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad No. 3000, Coyoacan CDMX 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucero","family":"Cuazozon-Ferrer","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Reprogramming, Department of Physiology, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad No. 3000, Coyoacan CDMX 04510, Mexico"},{"name":"Ingenieria en Biotecnolog\u00eda, Universidad Polit\u00e9cnica de Quintana Roo, Av. Arco Bicentenario, MZ. 11, Lote 1119-33 SM 255, Canc\u00fan Quintana Roo 77500, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-0610","authenticated-orcid":false,"given":"Maria-del-Carmen","family":"Silva-Lucero","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Reprogramming, Department of Physiology, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad No. 3000, Coyoacan CDMX 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres-Ivan","family":"Gutierrez-Malacara","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Reprogramming, Department of Physiology, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. 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Arco Bicentenario, MZ. 11, Lote 1119-33 SM 255, Canc\u00fan Quintana Roo 77500, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2497-1157","authenticated-orcid":false,"given":"Job-Al\u00ed","family":"D\u00edaz-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Ingenieria en Biotecnolog\u00eda, Universidad Polit\u00e9cnica de Quintana Roo, Av. Arco Bicentenario, MZ. 11, Lote 1119-33 SM 255, Canc\u00fan Quintana Roo 77500, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto-Alejandro","family":"Jim\u00e9nez-Orozco","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Universidad Nacional Aut\u00f3noma de Mexico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-2161","authenticated-orcid":false,"given":"Maria-del-Carmen","family":"Cardenas-Aguayo","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Reprogramming, Department of Physiology, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. 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