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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-06-1843. This Article Full Text (PDF) All Versions of this Article: 2002-06-1843v1 101/4/1591    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pastore, Y. D Articles by Prchal, J. T Search for Related Content PubMed PubMed Citation Articles by Pastore, Y. D Articles by Prchal, J. T Social Bookmarking                   What's this? Submitted June 24, 2002 Accepted August 29, 2002 Mutations in the VHL Gene in Sporadic Apparently Congenital Polycythemia Yves D Pastore, Jaroslav Jelinek, Sonny Ang, Yongli Guan, Enli Liu, Katerina Jedlickova, Lakshmanan Krishnamurti, and Josef T Prchal* Texas Children's Cancer Center & Hematology Service, Baylor College of Medicine, Houston, TX, USA Department of Hematology, Baylor College of Medicine, Houston, TX, USA Department of Pediatrics, University of Minnesota, Mineapolis, MN, USA Department of Hematology, Baylor College of Medicine, Houston, TX, USA; Texas Children's Cancer Center & Hematology Service, Baylor College of Medicine, Houston, TX, USA * Corresponding author; email: prchal{at}bcm.tmc.edu. The congenital polycythemic disorders with elevated erythropoietin (Epo) have been until recently an enigma, and abnormality in the hypoxia-sensing pathway has been hypothesized as a possible mechanism. The tumor suppressor von Hippel-Lindau (VHL) participates in the hypoxia-sensing pathway, as it binds to the proline-hydroxylated form of the hypoxia inducible factor-1 (HIF-1), mediates its ubiquitination and proteasomal degradation. The loss of VHL function may result in the accumulation of HIF-1 and overproduction of HIF-1 downstream target genes including Epo. Von Hippel-Lindau syndrome is an autosomal dominant disorder predisposing to the development of tumors, due to inherited mutations in the VHL gene. Some rare patients with VHL syndrome have polycythemia, which has been attributed to Epo production by a tumor. It was recently found that homozygosity for the VHL R200W mutation is the cause of Chuvash polycythemia, an autosomal recessive polycythemic disorder characterized by elevated serum Epo and hypersensitivity of erythroid cells to Epo. We evaluated the role of VHL in 8 children with a history of polycythemia and an elevated serum Epo, and found three different germ line VHL mutations in four of them. One child was homozygous for the R200W VHL mutation, and another a compound heterozygous for the R200W and the V130L mutations. Two children (siblings), were heterozygous for a D126Y mutation, one of them fulfilling some criteria of von Hippel-Lindau syndrome. We propose that mutations of the VHL gene represent an important cause of pediatric sporadic polycythemias with an inappropriately high serum Epo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Gergics, A. Patocs, M. Toth, P. Igaz, N. Szucs, I. Liko, F. Fazakas, I. Szabo, B. Kovacs, E. Glaz, et al. Germline VHL gene mutations in Hungarian families with von Hippel-Lindau disease and patients with apparently sporadic unilateral pheochromocytomas Eur. J. 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