303:(women). Angiomatosis occurs in 37.2% of patients presenting with VHL disease and usually occurs in the retina. As a result, loss of vision is very common. However, other organs can be affected: strokes, heart attacks, and cardiovascular disease are common additional symptoms. Approximately 40% of VHL disease presents with CNS hemangioblastomas and they are present in around 60–80%. Spinal hemangioblastomas are found in 13–59% of VHL disease and are specific because 80% are found in VHL disease. Although all of these tumors are common in VHL disease, around half of cases present with only one tumor type. Most people with VHL develop symptoms in their mid-twenties.
50:
137:
78:
582:, USA) are presumed to have VHL. In an article appearing in the Associated Press, it has been speculated by a Vanderbilt University endocrinologist that the hostility underlying the Hatfield–McCoy feud may have been partly due to the consequences of Von Hippel–Lindau disease. The article suggests that the McCoy family was predisposed to bad tempers because many of them had a pheochromocytoma that produced excess adrenaline and a tendency toward explosive tempers. An update of the Associated Press article in 2023 carries more details.
331:
254:
380:
539:
438:
and genes involved in glucose uptake and metabolism. A new novel missense mutation in VHL genes c.194 C>T, c.239 G>A, c.278 G>A, c.319 C>G, c.337 C>G leading to the following variations p.Ala 65 Val, p.Gly 80 Asp, p.Gly 93 Glu, p.Gln 107 Glu, p.Gln 113 Glu in the protein contributed
383:
The regulation of HIF1α by pVHL. Under normal oxygen levels, HIF1α binds pVHL through 2 hydroxylated proline residues and is polyubiquitinated by pVHL. This leads to its degradation via the proteasome. During hypoxia, the proline residues are not hydroxylated and pVHL cannot bind. HIF1α causes the
342:
Every cell in the body has two copies of every gene (bar those found in the sex chromosomes, X and Y). In VHL disease, one copy of the VHL gene has a mutation and produces a faulty VHL protein (pVHL). However, the second copy still produces a functional protein. The condition is inherited in an
491:
Early recognition and treatment of specific manifestations of VHL can substantially decrease complications and improve quality of life. For this reason, individuals with VHL disease are usually screened routinely for retinal angiomas, CNS hemangioblastomas, clear-cell renal carcinomas and
590:
Other uncommon names are: angiomatosis retinae, familial cerebello-retinal angiomatosis, cerebelloretinal hemangioblastomatosis, Hippel
Disease, Hippel–Lindau syndrome, HLS, VHL, Lindau disease or retinocerebellar angiomatosis.
426:. In low oxygen conditions or in cases of VHL disease where the VHL gene is mutated, pVHL does not bind to HIF1α. This allows the subunit to dimerise with HIF1β and activate the transcription of a number of genes, including
2275:
455:
may be sufficient to make a diagnosis. As all the tumours associated with VHL disease can be found sporadically, at least two tumours must be identified to diagnose VHL disease in a person without a family history.
1924:
1909:
1894:
1462:
Priesemann M; Davies KM; Perry LA; et al. (2006). "Benefits of screening in von Hippel-Lindau disease – comparison of morbidity associated with initial tumours in affected parents and children".
2268:
2261:
261:
Signs and symptoms associated with VHL disease include headaches, problems with balance and walking, dizziness, weakness of the limbs, vision problems, and high blood pressure.
384:
transcription of genes that contain the hypoxia response element. In VHL disease, genetic mutations cause alterations to the pVHL protein, usually to the HIF1α binding site.
500:
are usually used for the treatment of symptomatic retinal angiomas, although anti-angiogenic treatments may also be an option. Renal tumours may be removed by a partial
483:
VHL disease can be subdivided according to the clinical manifestations, although these groups often correlate with certain types of mutations present in the VHL gene.
1768:
447:
The detection of tumours specific to VHL disease is important in the disease's diagnosis. In individuals with a family history of VHL disease, one hemangioblastoma,
1838:
359:
that remove either part of the gene or the whole gene and flanking regions of DNA. The remaining 60-70% of VHL disease is caused by the truncation of pVHL by
1584:
719:
2342:
1536:
661:
840:
1060:
530:
by the age of 65. Age at diagnosis varies from infancy to age 60–70 years, with an average patient age at clinical diagnosis of 26 years.
403:
levels is highly regulated. In normal physiological conditions, pVHL recognizes and binds to HIF1α only when oxygen is present due to the
2324:
467:
can be used to analyse DNA and identify mutations. These tests can be used to screen family members of those afflicted with VHL disease;
2176:
2032:
2222:
2093:
312:
121:
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1626:
910:
820:
2242:
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17:
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are more difficult to detect because mutations are not found in the white blood cells that are used for genetic analysis.
2483:
1939:
1866:
1754:
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2436:
2048:
1833:
1323:
Kumar, P. S.; Venkatesh, K.; Srikanth, L.; Sarma, P. V.; Reddy, A. R.; Subramanian, S.; Phaneendra, B. V. (July 2013).
427:
1849:
1091:
1724:
1329:
1325:"Novel three missense mutations observed in Von Hippel-Lindau gene in a patient reported with renal cell carcinoma"
343:
autosomal dominant manner – one copy of the faulty gene is sufficient to increase the risk of developing tumours.
404:
2447:
2289:
2253:
1990:
2517:
2388:
786:
459:
Genetic diagnosis is also useful in VHL disease diagnosis. In hereditary VHL disease, techniques such as the
288:
1563:"Merck Receives Priority Review From FDA for New Drug Application for HIF-2α Inhibitor Belzutifan (MK-6482)"
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2181:
300:
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2150:
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636:
49:
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758:
615:
352:
mutations. An inherited mutation of the VHL gene is responsible for the remaining 80 percent of cases.
346:
Approximately 20% of cases of VHL disease are found in individuals without a family history, known as
2329:
2206:
2118:
845:
813:
Todd-Sanford clinical diagnosis by laboratory methods, edited by Israel
Davidsohn John Bernard Henry
605:
966:
734:"Von Hippel-Lindau disease | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program"
2201:
2037:
1950:
77:
136:
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pheochromocytomas. CNS hemangioblastomas are usually surgically removed if they are symptomatic.
292:
2567:
2378:
2285:
2232:
2146:
1903:
2227:
2079:
1755:
The
Hatfield-McCoy feud can in part be explained by a rare medical condition that causes rage
1419:
Calzada, MJ (March 2010). "Von Hippel-Lindau syndrome: molecular mechanisms of the disease".
713:
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316:
277:
8:
2522:
1928:
1047:
Friedrich, CA (December 1, 1999). "Von Hippel-Lindau syndrome. A pleomorphic condition".
575:
2015:
1109:
Kondo, K; Kaelin Jr, WG (10 March 2001). "The von Hippel–Lindau Tumor
Suppressor Gene".
514:
is a drug under investigation for the treatment of von Hippel–Lindau disease-associated
2572:
2319:
2141:
1706:
1702:
1671:
1585:"FDA Grants Priority Review to Belzutifan for von Hippel-Lindau Disease–Associated RCC"
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1401:
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1175:
1072:
1019:
994:
954:
867:
841:"Genotype–phenotype correlation in von Hippel–Lindau disease with retinal angiomatosis"
335:
144:
1933:
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62:
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2001:
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862:
854:
770:
693:
547:
493:
448:
324:
273:
269:
105:
67:
1689:
Lindau A (1927). "Zur Frage der
Angiomatosis Retinae und Ihrer Hirncomplikation".
1291:
2370:
2171:
1955:
1798:
1618:
1613:. Advances in Experimental Medicine and Biology. Vol. 685. pp. 228–49.
559:
2414:
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1966:
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1514:
858:
464:
435:
2026:
2004:
1918:
1827:
1432:
1144:
Nordstrom-O'Brien M; van der Luijt RB; van
Rooijen E; et al. (May 2010).
1061:
10.1002/(SICI)1097-0142(19991201)86:11+<2478::AID-CNCR4>3.0.CO;2-5
927:
2546:
1343:
460:
407:
393:
109:
57:
Locations of the main types of cysts and tumors in Von Hippel–Lindau disease.
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2110:
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1028:
939:
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705:
681:
551:
388:
The VHL protein (pVHL) is involved in the regulation of a protein known as
265:
125:
113:
102:
1010:
566:
was first used in 1936; however, its use became common only in the 1970s.
330:
2021:
1985:
1732:
900:
697:
501:
497:
526:
VHL disease has an incidence of one in 36,000 births. There is over 90%
112:
with potential for subsequent malignant transformation. It is a type of
108:
with multisystem involvement. It is characterized by visceral cysts and
2010:
1775:. NORD - National Organization for Rare Disorders. 2019. Archived from
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1464:
1162:
1145:
679:
579:
555:
527:
511:
423:
296:
281:
257:
Typical distribution of hemangioblastomas in Von Hippel–Lindau disease.
1886:
1476:
2424:
2133:
1996:
1206:
1193:
Knudson, AG (Nov 2001). "Two genetic hits (more or less) to cancer".
926:
Frantzen, Carlijn; Links, Thera P.; Giles, Rachel H. (21 June 2012).
419:
415:
140:
71:
1651:
1609:
Kim, JJ; Rini, BI; Hansel, DE (2010). "Von Hippel Lindau
Syndrome".
2303:
2054:
901:
Lindsay, Kenneth W; Ian Bone; Robin
Callander; J. van Gijn (1991).
348:
117:
759:"Von Hippel-Lindau: How a rare disease illuminates cancer biology"
610:
411:
1944:
1870:
253:
2071:
1913:
1898:
431:
379:
756:
2349:
1461:
995:"von Hippel-Lindau disease: a clinical and scientific review"
389:
364:
838:
2313:
2043:
1828:
GeneReviews/NCBI/NIH/UW entry on Von Hippel-Lindau
Syndrome
1537:"MHRA awards first 'innovation passport' under new pathway"
1322:
839:
Wong WT; Agrón E; Coleman HR; et al. (February 2007).
284:
992:
538:
993:
Maher ER; Glenn GM; Walther M; et al. (June 2011).
757:
Richard, S; Gardie, B; Couvé, S; Gad, S (May 30, 2012).
355:
30–40% of mutations in the VHL gene consist of 50-250kb
815:(14th ed.). Philadelphia: Saunders. p. 555.
574:
Some descendants of the McCoy family (involved in the
1608:
1876:
1376:
Lonser RR (June 2003). "von Hippel-Lindau disease".
811:
Henry, Todd; Campell, James; Hawley, Arthur (1969).
925:
810:
1652:"Ueber eine sehr seltene Erkrankung der Netzhaut"
1276:"Systemic VHL gene functions and the VHL disease"
2544:
1239:Kaelin, WG (2007). "Von Hippel-Lindau disease".
680:Leung RS, Biswas SV, Duncan M, Rankin S (2008).
2343:Leukoencephalopathy with vanishing white matter
1656:Albrecht von Graefe's Archiv für Ophthalmologie
1234:
1232:
1146:"Genetic analysis of von Hippel-Lindau disease"
1042:
1040:
1038:
682:"Imaging features of von Hippel-Lindau disease"
264:Conditions associated with VHL disease include
1108:
988:
986:
984:
982:
980:
978:
976:
414:residues within the HIF1α protein. pVHL is an
295:, and bilateral papillary cystadenomas of the
2269:
2087:
550:first described angiomas in the eye in 1904.
334:Von Hippel–Lindau disease is inherited in an
1727:Hatfield–McCoy feud blamed on 'rage' disease
1649:
1412:
1369:
1229:
1137:
1035:
718:: CS1 maint: multiple names: authors list (
542:Original Von Hippel's description of disease
2325:Fragile X-associated tremor/ataxia syndrome
1273:
973:
675:
673:
671:
660:: CS1 maint: numeric names: authors list (
2276:
2262:
2094:
2080:
311:The disease is caused by mutations of the
76:
1375:
1352:
1342:
1299:
1161:
1046:
1018:
866:
1758:, Aussociated Press (AP), August 4, 2023
1688:
905:. United States: Churchill Livingstone.
668:
537:
422:HIF1α and causes its degradation by the
378:
329:
252:
135:
1731:. MSNBC.com. 2007-04-05. Archived from
1418:
1192:
894:
210:Papillary cystadenoma of the epididymis
42:Familial cerebello retinal angiomatosis
14:
2545:
1752:Marchione, Marilynn; Breed, Allen G.,
1253:10.1146/annurev.pathol.2.010506.092049
1238:
1089:
903:Neurology and Neurosurgery Illustrated
834:
832:
2484:Multiple familial trichoepithelioma 1
2257:
2075:
1565:(Press release). Merck. 16 March 2016
1421:Clinical & Translational Oncology
934:. University of Washington, Seattle.
637:"Orphanet: Von Hippel Lindau disease"
131:
2243:Encephalocraniocutaneous lipomatosis
2049:acute-disseminated-encephalomyelitis
1529:
635:RESERVED, INSERM US14-- ALL RIGHTS.
634:
228:Neuroendocrine tumor of the pancreas
1867:Online Mendelian Inheritance in Man
1805:. U.S. National Library of Medicine
829:
24:
2437:X-linked spinal muscular atrophy 2
1703:10.1111/j.1755-3768.1926.tb07786.x
1274:Bader, HL; Hsu, T (June 4, 2012).
999:European Journal of Human Genetics
428:vascular endothelial growth factor
313:Von Hippel–Lindau tumor suppressor
236:Serous cystadenoma of the pancreas
122:Von Hippel–Lindau tumor suppressor
25:
2584:
2177:Bannayan–Riley–Ruvalcaba syndrome
1821:
1511:SPS - Specialist Pharmacy Service
1092:"Von Hippel-Lindau Disease (VHL)"
478:
2101:
1330:Indian Journal of Human Genetics
1090:Clinic, Cleveland (2017-10-16).
569:
432:platelet-derived growth factor B
392:(HIF1α). This is a subunit of a
48:
2223:Abdallat–Davis–Farrage syndrome
1834:Von Hippel–Lindau Disease (VHL)
1803:Medical Subject Headings (MeSH)
1791:
1761:
1746:
1717:
1682:
1643:
1602:
1577:
1555:
1513:. 18 March 2021. Archived from
1499:
1455:
1316:
1267:
1186:
1102:
1083:
775:10.1016/j.semcancer.2012.05.005
585:
521:
439:to renal clear cell carcinoma.
319:(3p25-26). There are over 1500
315:(VHL) gene on the short arm of
306:
2363:Posttranslational modification
2290:posttranslational modification
919:
804:
750:
726:
628:
554:described the angiomas of the
374:
150:
13:
1:
2518:Multiple sulfatase deficiency
2397:3-Methylglutaconic aciduria 5
1390:10.1016/S0140-6736(03)13643-4
1292:10.1016/j.febslet.2012.04.032
621:
289:pancreatic serous cystadenoma
2553:Autosomal dominant disorders
1619:10.1007/978-1-4419-6448-9_22
928:"Von Hippel-Lindau Syndrome"
504:or other techniques such as
486:
442:
301:broad ligament of the uterus
202:Spinal cord hemangioblastoma
147:in Von Hippel–Lindau disease
7:
2330:Premature ovarian failure 1
2162:Multiple hamartoma syndrome
1799:"von Hippel-Lindau Disease"
1769:"Von Hippel-Lindau Disease"
594:
546:The German ophthalmologist
390:hypoxia inducible factor 1α
170:Cerebellar hemangioblastoma
10:
2589:
2448:Johanson–Blizzard syndrome
2027:von Hippel-Lindau syndrome
1845:Von Hippel–Lindau syndrome
1573:– via Business Wire.
1241:Annual Review of Pathology
1111:Experimental Cell Research
859:10.1001/archopht.125.2.239
763:Seminars in Cancer Biology
616:Proximal convoluted tubule
533:
244:Medullary hemangioblastoma
2510:
2492:
2453:Von Hippel–Lindau disease
2423:
2405:
2389:Creutzfeldt–Jakob disease
2369:
2362:
2296:
2215:
2192:
2132:
2124:Von Hippel–Lindau disease
2109:
2038:von-hippel-lindau-disease
2016:Von Hippel–Lindau disease
1976:
1880:
1433:10.1007/s12094-010-0485-9
932:Von Hippel-Lindau Disease
846:Archives of Ophthalmology
738:rarediseases.info.nih.gov
606:Epithelial sodium channel
564:Von Hippel–Lindau disease
88:Von Hippel–Lindau disease
61:
56:
47:
37:
33:Von Hippel–Lindau disease
32:
2528:Ehlers–Danlos syndrome 6
2182:Lhermitte–Duclos disease
1344:10.4103/0971-6866.120809
186:Retinal hemangioblastoma
2470:Deubiquitinating enzyme
2354:Retinitis pigmentosa 33
2308:Diamond–Blackfan anemia
2151:Pallister–Hall syndrome
1852:Genetics Home Reference
506:radiofrequency ablation
293:endolymphatic sac tumor
2474:Machado–Joseph disease
2238:Peutz–Jeghers syndrome
2233:Incontinentia pigmenti
2147:Hypothalamic hamartoma
1991:vonhippellindaudisease
1611:Diseases of DNA Repair
1123:10.1006/excr.2000.5139
692:(1): 65–79, quiz 323.
543:
385:
339:
327:found in VHL disease.
258:
148:
99:Hippel–Lindau syndrome
2228:Ataxia telangiectasia
2119:Sturge–Weber syndrome
1857:Hippel–Lindau disease
1773:Rare Disease Database
1650:Von Hippel E (1904).
1195:Nature Reviews Cancer
1055:(11 Suppl): 2478–82.
1011:10.1038/ejhg.2010.175
541:
382:
369:splice site mutations
333:
256:
139:
2479:Aneurysmal bone cyst
2384:Huntington's disease
1691:Acta Ophthalmologica
698:10.1148/rg.281075052
516:renal cell carcinoma
453:renal cell carcinoma
397:transcription factor
278:renal cell carcinoma
194:Renal cell carcinoma
116:that results from a
18:Angiomatosis retinae
2523:Hyperproinsulinemia
2379:Alzheimer's disease
576:Hatfield-McCoy feud
471:cases that produce
143:photograph showing
2563:Hereditary cancers
2320:Fragile X syndrome
2142:Tuberous sclerosis
1977:External resources
1668:10.1007/bf01994821
1163:10.1002/humu.21219
562:in 1927. The term
544:
405:post translational
386:
361:nonsense mutations
357:deletion mutations
340:
336:autosomal dominant
321:germline mutations
259:
149:
145:retinal detachment
132:Signs and symptoms
2540:
2539:
2536:
2535:
2463:Angelman syndrome
2407:Protein targeting
2339:Initiation factor
2251:
2250:
2194:Neurofibromatosis
2069:
2068:
1628:978-1-4419-6447-2
1477:10.1159/000093008
1384:(9374): 2059–67.
912:978-0-443-04345-1
822:978-0-7216-2921-6
601:Haemangioblastoma
473:genetic mosaicism
325:somatic mutations
270:hemangioblastomas
251:
250:
94:), also known as
85:
84:
27:Medical condition
16:(Redirected from
2580:
2367:
2366:
2278:
2271:
2264:
2255:
2254:
2167:Proteus syndrome
2096:
2089:
2082:
2073:
2072:
1878:
1877:
1815:
1814:
1812:
1810:
1795:
1789:
1788:
1786:
1784:
1779:on 25 April 2015
1765:
1759:
1750:
1744:
1743:
1741:
1740:
1721:
1715:
1714:
1697:(1–2): 193–226.
1686:
1680:
1679:
1647:
1641:
1640:
1606:
1600:
1599:
1597:
1596:
1581:
1575:
1574:
1572:
1570:
1559:
1553:
1552:
1550:
1548:
1533:
1527:
1526:
1524:
1522:
1517:on 26 April 2021
1503:
1497:
1496:
1459:
1453:
1452:
1416:
1410:
1409:
1373:
1367:
1366:
1356:
1346:
1320:
1314:
1313:
1303:
1271:
1265:
1264:
1236:
1227:
1226:
1207:10.1038/35101031
1190:
1184:
1183:
1165:
1141:
1135:
1134:
1106:
1100:
1099:
1096:Cleveland Clinic
1087:
1081:
1080:
1044:
1033:
1032:
1022:
990:
971:
970:
964:
960:
958:
950:
948:
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923:
917:
916:
898:
892:
891:
889:
888:
879:. Archived from
870:
836:
827:
826:
808:
802:
801:
799:
797:
792:on April 9, 2022
791:
785:. Archived from
754:
748:
747:
745:
744:
730:
724:
723:
717:
709:
677:
666:
665:
659:
651:
649:
647:
632:
548:Eugen von Hippel
494:Photocoagulation
449:pheochromocytoma
274:pheochromocytoma
220:Pheochromocytoma
162:Pancreatic cysts
151:
106:genetic disorder
81:
80:
68:Medical genetics
52:
30:
29:
21:
2588:
2587:
2583:
2582:
2581:
2579:
2578:
2577:
2543:
2542:
2541:
2532:
2506:
2488:
2419:
2401:
2371:Protein folding
2358:
2292:
2282:
2252:
2247:
2211:
2188:
2172:Cowden syndrome
2128:
2105:
2100:
2070:
2065:
2064:
1972:
1971:
1889:
1824:
1819:
1818:
1808:
1806:
1797:
1796:
1792:
1782:
1780:
1767:
1766:
1762:
1751:
1747:
1738:
1736:
1723:
1722:
1718:
1687:
1683:
1648:
1644:
1629:
1607:
1603:
1594:
1592:
1591:. 16 March 2021
1583:
1582:
1578:
1568:
1566:
1561:
1560:
1556:
1546:
1544:
1543:(Press release)
1535:
1534:
1530:
1520:
1518:
1505:
1504:
1500:
1460:
1456:
1417:
1413:
1374:
1370:
1321:
1317:
1272:
1268:
1237:
1230:
1191:
1187:
1142:
1138:
1107:
1103:
1088:
1084:
1045:
1036:
991:
974:
962:
961:
952:
951:
944:
942:
924:
920:
913:
899:
895:
886:
884:
837:
830:
823:
809:
805:
795:
793:
789:
755:
751:
742:
740:
732:
731:
727:
711:
710:
678:
669:
653:
652:
645:
643:
633:
629:
624:
597:
588:
572:
536:
524:
489:
481:
465:gene sequencing
445:
401:cellular oxygen
399:that at normal
377:
365:indel mutations
309:
214:
154:Tumor/cyst type
134:
75:
28:
23:
22:
15:
12:
11:
5:
2586:
2576:
2575:
2570:
2565:
2560:
2558:Genodermatoses
2555:
2538:
2537:
2534:
2533:
2531:
2530:
2525:
2520:
2514:
2512:
2508:
2507:
2505:
2504:
2498:
2496:
2490:
2489:
2487:
2486:
2481:
2476:
2466:
2465:
2460:
2455:
2450:
2440:
2439:
2429:
2427:
2421:
2420:
2418:
2417:
2415:I-cell disease
2411:
2409:
2403:
2402:
2400:
2399:
2392:
2391:
2386:
2381:
2375:
2373:
2364:
2360:
2359:
2357:
2356:
2346:
2345:
2335:
2334:
2333:
2332:
2327:
2322:
2310:
2300:
2298:
2294:
2293:
2281:
2280:
2273:
2266:
2258:
2249:
2248:
2246:
2245:
2240:
2235:
2230:
2225:
2219:
2217:
2213:
2212:
2210:
2209:
2204:
2198:
2196:
2190:
2189:
2187:
2186:
2185:
2184:
2179:
2174:
2169:
2159:
2157:Megalencephaly
2154:
2144:
2138:
2136:
2130:
2129:
2127:
2126:
2121:
2115:
2113:
2107:
2106:
2099:
2098:
2091:
2084:
2076:
2067:
2066:
2063:
2062:
2051:
2040:
2029:
2018:
2007:
1993:
1981:
1980:
1978:
1974:
1973:
1970:
1969:
1958:
1947:
1936:
1921:
1906:
1890:
1885:
1884:
1882:
1881:Classification
1875:
1874:
1864:
1853:
1841:
1830:
1823:
1822:External links
1820:
1817:
1816:
1790:
1760:
1745:
1716:
1681:
1642:
1627:
1601:
1589:Cancer Network
1576:
1554:
1528:
1498:
1454:
1411:
1368:
1337:(3): 373–376.
1315:
1286:(11): 1562–9.
1266:
1228:
1185:
1136:
1117:(1): 117–125.
1101:
1082:
1034:
972:
918:
911:
893:
828:
821:
803:
749:
725:
667:
626:
625:
623:
620:
619:
618:
613:
608:
603:
596:
593:
587:
584:
571:
568:
535:
532:
523:
520:
488:
485:
480:
479:Classification
477:
444:
441:
436:erythropoietin
376:
373:
308:
305:
249:
248:
245:
241:
240:
237:
233:
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221:
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133:
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83:
82:
65:
59:
58:
54:
53:
45:
44:
39:
35:
34:
26:
9:
6:
4:
3:
2:
2585:
2574:
2571:
2569:
2568:Rare diseases
2566:
2564:
2561:
2559:
2556:
2554:
2551:
2550:
2548:
2529:
2526:
2524:
2521:
2519:
2516:
2515:
2513:
2509:
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2500:
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2497:
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2431:
2430:
2428:
2426:
2422:
2416:
2413:
2412:
2410:
2408:
2404:
2398:
2395:chaperonins:
2394:
2393:
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2387:
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2380:
2377:
2376:
2374:
2372:
2368:
2365:
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2318:
2317:
2316:
2315:
2311:
2309:
2305:
2302:
2301:
2299:
2295:
2291:
2287:
2284:Disorders of
2279:
2274:
2272:
2267:
2265:
2260:
2259:
2256:
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2239:
2236:
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2163:
2160:
2158:
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2112:
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2097:
2092:
2090:
2085:
2083:
2078:
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2074:
2061:
2057:
2056:
2052:
2050:
2046:
2045:
2041:
2039:
2035:
2034:
2030:
2028:
2024:
2023:
2019:
2017:
2013:
2012:
2008:
2006:
2003:
1999:
1998:
1994:
1992:
1988:
1987:
1983:
1982:
1979:
1975:
1968:
1964:
1963:
1959:
1957:
1953:
1952:
1948:
1946:
1942:
1941:
1937:
1935:
1931:
1930:
1926:
1922:
1920:
1916:
1915:
1911:
1907:
1905:
1901:
1900:
1896:
1892:
1891:
1888:
1883:
1879:
1872:
1868:
1865:
1863:
1862:Who Named It?
1859:
1858:
1854:
1851:
1847:
1846:
1842:
1840:
1836:
1835:
1831:
1829:
1826:
1825:
1804:
1800:
1794:
1778:
1774:
1770:
1764:
1757:
1756:
1749:
1735:on 2007-04-07
1734:
1730:
1728:
1720:
1712:
1708:
1704:
1700:
1696:
1692:
1685:
1677:
1673:
1669:
1665:
1661:
1657:
1653:
1646:
1638:
1634:
1630:
1624:
1620:
1616:
1612:
1605:
1590:
1586:
1580:
1564:
1558:
1542:
1538:
1532:
1516:
1512:
1508:
1502:
1494:
1490:
1486:
1482:
1478:
1474:
1470:
1467:
1466:
1458:
1450:
1446:
1442:
1438:
1434:
1430:
1426:
1422:
1415:
1407:
1403:
1399:
1395:
1391:
1387:
1383:
1379:
1372:
1364:
1360:
1355:
1350:
1345:
1340:
1336:
1332:
1331:
1326:
1319:
1311:
1307:
1302:
1297:
1293:
1289:
1285:
1281:
1277:
1270:
1262:
1258:
1254:
1250:
1246:
1242:
1235:
1233:
1224:
1220:
1216:
1212:
1208:
1204:
1201:(2): 157–62.
1200:
1196:
1189:
1181:
1177:
1173:
1169:
1164:
1159:
1156:(5): 521–37.
1155:
1151:
1147:
1140:
1132:
1128:
1124:
1120:
1116:
1112:
1105:
1097:
1093:
1086:
1078:
1074:
1070:
1066:
1062:
1058:
1054:
1050:
1043:
1041:
1039:
1030:
1026:
1021:
1016:
1012:
1008:
1005:(6): 617–23.
1004:
1000:
996:
989:
987:
985:
983:
981:
979:
977:
968:
956:
941:
937:
933:
929:
922:
914:
908:
904:
897:
883:on 2008-12-12
882:
878:
874:
869:
864:
860:
856:
853:(2): 239–45.
852:
848:
847:
842:
835:
833:
824:
818:
814:
807:
788:
784:
780:
776:
772:
768:
764:
760:
753:
739:
735:
729:
721:
715:
707:
703:
699:
695:
691:
687:
686:Radiographics
683:
676:
674:
672:
663:
657:
642:
641:www.orpha.net
638:
631:
627:
617:
614:
612:
609:
607:
604:
602:
599:
598:
592:
583:
581:
577:
570:Notable cases
567:
565:
561:
557:
553:
549:
540:
531:
529:
519:
517:
513:
509:
507:
503:
499:
495:
484:
476:
474:
470:
466:
462:
461:Southern blot
457:
454:
450:
440:
437:
433:
429:
425:
421:
420:ubiquitinates
417:
413:
409:
408:hydroxylation
406:
402:
398:
395:
394:heterodimeric
391:
381:
372:
370:
366:
362:
358:
353:
351:
350:
344:
337:
332:
328:
326:
322:
318:
314:
304:
302:
298:
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290:
286:
283:
279:
275:
271:
267:
262:
255:
246:
243:
242:
238:
235:
234:
230:
227:
226:
222:
219:
218:
212:
209:
208:
204:
201:
200:
196:
193:
192:
188:
185:
184:
180:
177:
176:
172:
169:
168:
164:
161:
160:
156:
153:
152:
146:
142:
138:
129:
127:
126:chromosome 3p
123:
119:
115:
111:
110:benign tumors
107:
104:
100:
97:
93:
89:
79:
73:
69:
66:
64:
60:
55:
51:
46:
43:
40:
36:
31:
19:
2458:3-M syndrome
2452:
2312:
2123:
2111:Angiomatosis
2103:Phakomatosis
2053:
2042:
2031:
2020:
2009:
1995:
1984:
1960:
1949:
1938:
1923:
1908:
1893:
1855:
1843:
1832:
1807:. Retrieved
1802:
1793:
1781:. Retrieved
1777:the original
1772:
1763:
1753:
1748:
1737:. Retrieved
1733:the original
1726:
1719:
1694:
1690:
1684:
1659:
1655:
1645:
1610:
1604:
1593:. Retrieved
1588:
1579:
1567:. Retrieved
1557:
1545:. Retrieved
1540:
1531:
1519:. Retrieved
1515:the original
1510:
1507:"Belzutifan"
1501:
1468:
1463:
1457:
1427:(3): 160–5.
1424:
1420:
1414:
1381:
1377:
1371:
1334:
1328:
1318:
1283:
1280:FEBS Letters
1279:
1269:
1244:
1240:
1198:
1194:
1188:
1153:
1149:
1139:
1114:
1110:
1104:
1095:
1085:
1052:
1048:
1002:
998:
943:. Retrieved
931:
921:
902:
896:
885:. Retrieved
881:the original
850:
844:
812:
806:
794:. Retrieved
787:the original
769:(1): 26–37.
766:
762:
752:
741:. Retrieved
737:
728:
714:cite journal
689:
685:
644:. Retrieved
640:
630:
589:
586:Nomenclature
573:
563:
552:Arvid Lindau
545:
525:
522:Epidemiology
510:
490:
482:
468:
458:
446:
387:
354:
347:
345:
341:
317:chromosome 3
310:
307:Pathogenesis
266:angiomatosis
263:
260:
114:phakomatosis
98:
95:
91:
87:
86:
41:
2297:Translation
2286:translation
2022:GeneReviews
1986:MedlinePlus
963:|work=
502:nephrectomy
498:cryotherapy
375:VHL protein
178:Renal cysts
157:Prevalence
38:Other names
2547:Categories
2011:Patient UK
1962:DiseasesDB
1873:(VHL gene)
1739:2007-04-05
1662:: 83–106.
1595:2021-04-26
1471:(1): 1–5.
1465:Horm. Res.
1247:: 145–73.
1150:Hum. Mutat
887:2008-10-22
743:2018-04-17
622:References
580:Appalachia
556:cerebellum
528:penetrance
512:Belzutifan
424:proteasome
297:epididymis
282:pancreatic
2573:Syndromes
2425:Ubiquitin
2134:Hamartoma
1997:eMedicine
965:ignored (
955:cite book
796:April 20,
487:Treatment
443:Diagnosis
416:E3 ligase
299:(men) or
215:of males
141:Slit lamp
72:neurology
63:Specialty
2304:Ribosome
2055:Orphanet
2002:ped/2417
1869:(OMIM):
1711:73385451
1676:22425158
1637:20687511
1569:25 April
1547:25 April
1521:25 April
1493:29862078
1485:16651847
1441:20231120
1406:13783714
1398:12814730
1363:24339559
1310:22673568
1261:18039096
1223:20201610
1215:11905807
1180:38910112
1172:20151405
1131:11237528
1077:45672391
1069:10630173
1029:21386872
945:30 March
940:20301636
877:17296901
783:22659535
706:18203931
656:cite web
595:See also
338:pattern.
124:gene on
118:mutation
2207:Type II
2005:oph/354
1956:D006623
1809:4 April
1783:4 April
1449:7789108
1354:3841571
1301:3372859
1020:3110036
868:3019103
611:Nephron
534:History
469:de novo
412:proline
349:de novo
205:13-59%
197:24-45%
189:45-59%
181:59-63%
173:44-72%
165:50-91%
120:in the
101:, is a
2202:Type I
1945:193300
1871:608537
1709:
1674:
1635:
1625:
1491:
1483:
1447:
1439:
1404:
1396:
1378:Lancet
1361:
1351:
1308:
1298:
1259:
1221:
1213:
1178:
1170:
1129:
1075:
1067:
1049:Cancer
1027:
1017:
938:
909:
875:
865:
819:
781:
704:
646:25 May
231:5-17%
223:0-60%
213:10-60%
128:25.3.
74:
2511:Other
2502:OFC10
2350:snRNP
2216:Other
1967:14000
1934:759.6
1919:Q85.8
1839:NINDS
1707:S2CID
1672:S2CID
1489:S2CID
1445:S2CID
1402:S2CID
1219:S2CID
1176:S2CID
1073:S2CID
790:(PDF)
560:spine
418:that
410:of 2
285:cysts
2494:SUMO
2314:FMR1
2288:and
2044:GARD
2033:NORD
1951:MeSH
1940:OMIM
1929:9-CM
1904:5A75
1811:2022
1785:2022
1633:PMID
1623:ISBN
1571:2021
1549:2021
1541:RAPS
1523:2021
1481:PMID
1437:PMID
1394:PMID
1359:PMID
1306:PMID
1257:PMID
1211:PMID
1168:PMID
1127:PMID
1065:PMID
1025:PMID
967:help
947:2013
936:PMID
907:ISBN
873:PMID
817:ISBN
798:2018
779:PMID
720:link
702:PMID
662:link
648:2019
558:and
496:and
463:and
323:and
239:12%
103:rare
2060:892
1925:ICD
1910:ICD
1895:ICD
1860:at
1850:NLM
1848:at
1837:at
1699:doi
1664:doi
1615:doi
1473:doi
1429:doi
1386:doi
1382:361
1349:PMC
1339:doi
1296:PMC
1288:doi
1284:586
1249:doi
1203:doi
1158:doi
1119:doi
1115:264
1057:doi
1015:PMC
1007:doi
863:PMC
855:doi
851:125
771:doi
694:doi
578:of
451:or
367:or
291:),
247:5%
96:Von
92:VHL
2549::
2472::
2446::
2444:E3
2435::
2433:E1
2352::
2341::
2306::
2058::
2047::
2036::
2025::
2014::
2000::
1989::
1965::
1954::
1943::
1932::
1917::
1914:10
1902::
1899:11
1801:.
1771:.
1705:.
1693:.
1670:.
1660:59
1658:.
1654:.
1631:.
1621:.
1587:.
1539:.
1509:.
1487:.
1479:.
1469:66
1443:.
1435:.
1425:12
1423:.
1400:.
1392:.
1380:.
1357:.
1347:.
1335:19
1333:.
1327:.
1304:.
1294:.
1282:.
1278:.
1255:.
1243:.
1231:^
1217:.
1209:.
1197:.
1174:.
1166:.
1154:31
1152:.
1148:.
1125:.
1113:.
1094:.
1071:.
1063:.
1053:86
1051:.
1037:^
1023:.
1013:.
1003:19
1001:.
997:.
975:^
959::
957:}}
953:{{
930:.
871:.
861:.
849:.
843:.
831:^
777:.
767:23
765:.
761:.
736:.
716:}}
712:{{
700:.
690:28
688:.
684:.
670:^
658:}}
654:{{
639:.
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1927:-
1912:-
1897:-
1887:D
1813:.
1787:.
1742:.
1729:"
1725:"
1713:.
1701::
1695:4
1678:.
1666::
1639:.
1617::
1598:.
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1495:.
1475::
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1431::
1408:.
1388::
1365:.
1341::
1312:.
1290::
1263:.
1251::
1245:2
1225:.
1205::
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1182:.
1160::
1133:.
1121::
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1079:.
1059::
1031:.
1009::
969:)
949:.
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