title: The homozygous VHL(D126N) missense mutation is associated with dramatically elevated erythropoietin levels, consequent polycythemia, and early onset severe pulmonary hypertension.
abstract: von Hippel-Lindau (VHL) protein is the principal negative regulator of hypoxia sensing mediated by transcription factors. Mutations in exon 3 of the VHL gene lead to Chuvash (VHL(R200W)) and Croatian (VHL(H191D)) polycythemias. Here, we describe an infant of Bangladesh ethnicity with a novel homozygous VHL(D126N) mutation with congenital polycythemia and dramatically elevated erythropoietin (EPO) levels, who developed severe fatal pulmonary hypertension. In contrast to Chuvash polycythemia, erythroid progenitors (BFU-Es) did not reveal a marked EPO hypersensitivity. Further, NF-E2 and RUNX1 transcripts that correlate with BFU-Es EPO hypersensitivity in polycythemic mutations were not elevated.
authors.affiliation: Division of Pediatric Hematology Oncology, Cohen Children's Medical Center, New Hyde Park, New York.
authors.forename: Susmita
authors.initials: S
authors.lastname: Sarangi
authors.forename: Lucie
authors.initials: L
authors.lastname: Lanikova
authors.forename: Katarina
authors.initials: K
authors.lastname: Kapralova
authors.forename: Suchitra
authors.initials: S
authors.lastname: Acharya
authors.forename: Sabina
authors.initials: S
authors.lastname: Swierczek
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Lipton
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wolfe
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D004921:Erythropoietin / Q000097:blood*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D011086:Polycythemia / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: C554270:EPO protein, human; D004921:Erythropoietin; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
keywords: erythropoietin; polycythemia; pulmonary hypertension; von Hippel-Lindau gene