Abstract
Prolyl hydroxylase domain (PHD) proteins play a major role in regulating the hypoxia-inducible factor (HIF) that induces expression of genes involved in angiogenesis, erythropoiesis, and cell metabolism, proliferation, and survival. Germ-line mutations in the prolyl hydroxylase domain 2 gene (PHD2) have been reported in patients with familial erythrocytosis but not in association with tumors. We describe a patient with erythrocytosis and recurrent paraganglioma who carries a newly discovered PHD2 mutation. This mutation affects PHD2 function and stabilizes HIF-alpha proteins. In addition, we demonstrate loss of heterozygosity of PHD2 in the tumor, suggesting that PHD2 could be a tumor-suppressor gene.
2008 Massachusetts Medical Society
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Female
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Germ-Line Mutation*
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Hemochromatosis Protein
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Histocompatibility Antigens Class I / genetics
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Homozygote
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Humans
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Hypoxia-Inducible Factor-Proline Dioxygenases
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Loss of Heterozygosity*
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Male
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Mediastinal Neoplasms / genetics*
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Membrane Proteins / genetics
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Neoplasms, Second Primary / genetics
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Paraganglioma / genetics*
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Pedigree
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Polycythemia / congenital
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Polycythemia / diagnosis
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Polycythemia / genetics*
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Procollagen-Proline Dioxygenase / genetics*
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Procollagen-Proline Dioxygenase / metabolism
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Sequence Analysis, DNA
Substances
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HFE protein, human
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Hemochromatosis Protein
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Histocompatibility Antigens Class I
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Membrane Proteins
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EGLN1 protein, human
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Procollagen-Proline Dioxygenase
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Hypoxia-Inducible Factor-Proline Dioxygenases