Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus

Neumann, Hartmut P. H.; Od, Wiestler

doi:10.1016/0140-6736(91)91705-y

Cited by 303 publications

(186 citation statements)

References 19 publications

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“…The onset of VHL disease occurs at a mean age of 26 years [Maher et al, 1990b]. VHL patients can develop hemangioblastomas of the central nervous system (CNS) and/or retina, clear cell renal cell carcinomas (RCC), endocrine neoplasia of the adrenal gland (pheochromocytoma), low-grade adenocarcinomas of the temporal bone, also known as endolymphatic sac tumors (ELST), epididymal or broad ligament cystadenomas, and/or pancreatic tumors [Gruber et al, 1980;Kaelin, 2007;Maher, 2004;Neumann and Wiestler, 1991]. In addition to the inherited risk for developing cancer, VHL patients develop cystic disease in various organs including the kidney, pancreas, and liver [Hough et al, 1994;Lubensky et al, 1998;Maher et al, 1990b;Maher, 2004].…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of von Hippel-Lindau disease

et al. 2010

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Mutations in the von Hippel-Lindau (VHL) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types as well. Reports of VHL mutations are dispersed throughout original articles and databases that have not been recently updated. We compiled a comprehensive mutation table of 1,548 germline and somatic VHL mutations, derived from this protein of only 213 amino acids. We describe detailed phenotype and gene mutation information for 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). These data represent the most extensive catalog of germline VHL mutations to date. We also review VHL disease, known and theorized pathogenesis of common VHL manifestations, and genotype-phenotype correlations. Analysis of all VHL families, excluding germline mutations resulting in congenital polycythemias, describes the spectrum of mutation types: 52% missense, 13% frameshift, 11% nonsense, 6% in-frame deletions/insertions, 11% large/complete deletions, and 7% splice mutations. This easy-to-use compilation of VHL mutations is intended to facilitate research and function as a necessary adjunct for physicians when providing patient information. Hum Mutat 31:521-537,

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Section: Introductionmentioning

confidence: 99%

Genetic analysis of von Hippel-Lindau disease

et al. 2010

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“…O produto do gene de VHL (pVHL), uma proteína de 284 aminoácidos e peso molecular de 18-23 Kd, regula a angiogênese, a formação da matriz e o ciclo celular. Mutações do gene de VHL permitem a estabilização da transcrição de fatores induzíveis pela hipóxia, e o aumento desses fatores angiogênicos, sob condições de normoxemia, acarreta a aparição das lesões altamente vasculares, patognomônicas da enfermidade 27,29 . Os indivíduos afetados estão em risco de desenvolver seis diferentes tipos de lesões cardinais: hemangioblastomas do SNC e retinianos, cistos ou carcinomas renais e pancreáticos, feocromocitomas e tumores do saco endolinfático 7,8,12,14,[18][19][20][21][27][28][29] .…”

Section: Discussionunclassified

“…Os indivíduos afetados estão em risco de desenvolver seis diferentes tipos de lesões cardinais: hemangioblastomas do SNC e retinianos, cistos ou carcinomas renais e pancreáticos, feocromocitomas e tumores do saco endolinfático 7,8,12,14,[18][19][20][21][27][28][29] . Os critérios diagnósticos, segundo Melmon e Rosen, modificados por Neumann [27][28][29][30] , incluem hemangioblastomas múltiplos ou um hemangioblastoma mais uma lesão visceral maior.…”

Section: Discussionunclassified

“…Na presença de história familiar positiva, que é possível reconhecer, segundo a literatura mundial 12,18,27 , em 80% dos casos, uma lesão maior é suficiente para estabelecer o diagnóstico clínico.…”

Section: Discussionunclassified

“…Os pacientes com lesões típicas, porém com história familiar negativa, deverão ser considerados portadores de uma mutação "de novo" 20,21,27,29 .…”

Section: Discussionunclassified

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