Primary familial polycythemia: A frameshift mutation in the erythropoietin receptor gene and increased sensitivity of erythroid progenitors to erythropoietin

L. Sokol, M. Luhovy, Y. Guan, J. F. Prchal, Gregg L Semenza, J. T. Prchal

Research output: Contribution to journalArticle

Abstract

Primary familial and congenital polycythemia (PFCP) is characterized by erythrocytosis with normal arterial PO2, blood P50, and serum erythropoietin (EPO) levels. In two PFCP families EPO receptor (EPOR) polymorphisms cosegregated with PFCP. A heterozygous insertion of G at EPOR nucleotide 5975 was identified in genomic DNA from polycythemic members of family no. 2. 5974insG shifts the reading frame at codon 430, predicting amino acid substitutions and truncation of the last 64 amino acids. Wild- type and mutant EPOR transcripts were detected in erythroid progenitors from affected individuals. Burst-forming units-erythroid from patients exhibited increased colony size and sensitivity to EPO. Transfected Ba/F3 cells expressing EPOR 5974insG exhibited increased EPO sensitivity compared with cells expressing wild-type EPOR. The functional effect of this EPOR mutation was directly compared with the other C-terminal mutations reported in unrelated PFCP families by expression in Ba/F3 cells. The transfected cells with another primary polycythemia associated EPOR mutant construct (G6002A) also exhibited increased sensitivity to EPO.

Original languageEnglish (US)
Pages (from-to)15-22
Number of pages8
JournalBlood
Volume86
Issue number1
StatePublished - 1995
Externally publishedYes

Fingerprint

Erythropoietin Receptors
Frameshift Mutation
Erythropoietin
Genes
Cells
Amino Acids
Reading Frames
Polycythemia Vera
Polycythemia
Erythroid Precursor Cells
Mutation
Amino Acid Substitution
Polymorphism
Codon
Blood
Substitution reactions
Nucleotides
Primary familial and congenital Polycythemia
DNA
Serum

ASJC Scopus subject areas

  • Hematology

Cite this

Primary familial polycythemia : A frameshift mutation in the erythropoietin receptor gene and increased sensitivity of erythroid progenitors to erythropoietin. / Sokol, L.; Luhovy, M.; Guan, Y.; Prchal, J. F.; Semenza, Gregg L; Prchal, J. T.

In: Blood, Vol. 86, No. 1, 1995, p. 15-22.

Research output: Contribution to journalArticle

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