2. Academic Validation
  3. A Gain-of-Function Mutation in EPO in Familial Erythrocytosis

A Gain-of-Function Mutation in EPO in Familial Erythrocytosis

  • N Engl J Med. 2018 Mar 8;378(10):924-930. doi: 10.1056/NEJMoa1709064.
Jakub Zmajkovic 1,  Pontus Lundberg 1,  Ronny Nienhold 1,  Maria L Torgersen 1,  Anders Sundan 1,  Anders Waage 1,  Radek C Skoda 1
Affiliations

Affiliation

  • 1 From the Department of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel (J.Z., P.L., R.N., R.C.S.), and Diagnostic Hematology, University Hospital Basel (P.L.), Basel, Switzerland; and the Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (M.L.T., A.S., A.W.), and the Department of Hematology, St. Olavs Hospital (A.W.) - both in Trondheim, Norway.
PMID: 29514032 DOI: 10.1056/NEJMoa1709064
Abstract

Familial erythrocytosis with elevated erythropoietin levels is frequently caused by mutations in genes that regulate oxygen-dependent transcription of the gene encoding erythropoietin ( EPO). We identified a mutation in EPO that cosegregated with disease with a logarithm of the odds (LOD) score of 3.3 in a family with autosomal dominant erythrocytosis. This mutation, a single-nucleotide deletion (c.32delG), introduces a frameshift in exon 2 that interrupts translation of the main EPO messenger RNA (mRNA) transcript but initiates excess production of erythropoietin from what is normally a noncoding EPO mRNA transcribed from an alternative promoter located in intron 1. (Funded by the Gebert Rüf Foundation and Others.).

Figures