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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 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 Citation Map 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. Related Collections Red Cells Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 February 2003, Vol. 101, No. 4, pp. 1591-1595 RED CELLS 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 From the Texas Children's Cancer Center and Hematology Service, Houston; Baylor College of Medicine and Veterans Administration Hospital, Houston, TX; and University of Minnesota, Minneapolis. 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) and mediates its ubiquitination and proteosomal degradation. The loss of VHL function may result in the accumulation of HIF-1 and overproduction of HIF-1 downstream target genes including Epo. VHL 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 Arg200Trp 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 level and found 3 different germline VHL mutations in 4 of them. One child was homozygous for the Arg200Trp VHL mutation, and another compound heterozygous for the Arg200Trp and the Val130Leu mutations. Two children (siblings) were heterozygous for an Asp126Tyr mutation, one of them fulfilling some criteria of VHL syndrome. We propose that mutations of the VHL gene represent an important cause of pediatric sporadic polycythemias with an inappropriately high serum Epo concentration. © 2003 by The American Society of Hematology.   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. 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