title: Isolated erythrocytosis: study of 67 patients and identification of three novel germ-line mutations in the prolyl hydroxylase domain protein 2 (PHD2) gene.
abstract: The oxygen sensing pathway modulates erythropoietin expression. In normal cells, intracellular oxygen tensions are directly sensed by prolyl hydroxylase domain (PHD)-containing proteins. PHD2 isozyme has a key role in tagging hypoxia-inducible factor (HIF)-α subunits for polyubiquitination and proteasomal degradation. Erythrocytosis-associated PHD2 mutations reduce hydroxylation of HIF-α. The investigation of 67 patients with isolated erythrocytosis, either sporadic or familial, allowed the identification of three novel mutations in the catalytic domain of the PHD2 protein. All new mutations are germ-line, heterozygous and missense, and code for a predicted full length mutant PHD2 protein. Identification of the disease-causing genes will be of critical importance for a better classification of familial and acquired erythrocytosis, offering additional insight into the erythropoietin regulating oxygen sensing pathway.
authors.affiliation: Department of Cellular Therapies and Haematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Albiero
authors.forename: Marco
authors.initials: M
authors.lastname: Ruggeri
authors.forename: Stefania
authors.initials: S
authors.lastname: Fortuna
authors.forename: Silvia
authors.initials: S
authors.lastname: Finotto
authors.forename: Martina
authors.initials: M
authors.lastname: Bernardi
authors.forename: Domenico
authors.initials: D
authors.lastname: Madeo
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001483:Base Sequence; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D011086:Polycythemia / Q000235:genetics*; D011393:Procollagen-Proline Dioxygenase / Q000737:chemistry / Q000235:genetics*; D011487:Protein Conformation
chemical_list: C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases