A newly-discovered hereditary mutation is responsible for an increased production of erythropoietin (EPO) in the blood. This mutation causes a messenger RNA (mRNA) that is not normally involved in the formation of proteins to be reprogrammed so that it produces EPO, thus abnormally increasing the number of red blood cells. Researchers from the Department of Biomedicine at the University of Basel and University Hospital Basel reported these findings in The New England Journal of Medicine.
In patients suffering from erythrocytosis, the red blood cell mass (erythrocytes) is exceptionally high. The disease is usually triggered by a genetic disorder in the bone marrow, which leads to increased production of red blood cells.
Researchers from the University of Basel and University Hospital Basel have now identified the first mutation in the EPO gene in a family with hereditary erythrocytosis. Ten affected family members from four generations took part in the study.
Using a genome-wide linkage analysis and gene sequencing, the researchers discovered that all of the affected family members lacked a single base in the EPO gene. As the EPO hormone increases the production of red blood cells, it was likely that this mutation caused the disease.
Overproduction instead of failure
However, the researchers were initially puzzled. This mutation would actually lead to a loss of function of the EPO gene, because the absence of the base shifts the reading frame of the genetic code, meaning that no more EPO protein can be formed. Despite this, the concentration of EPO hormone in the patients’ blood measurably increased rather than decreased.
The explanation was found using the CRISPR method, which allowed the researchers to engineer cells carrying the EPO mutation. There is a second, hidden mRNA in the EPO gene that is not normally involved in the production of a protein. As the researchers show, the mutation also leads to a shift in the reading frame of this second mRNA, this time with the result that more biologically active EPO hormone is produced.
“The mechanism is intriguing,” says study leader Professor Radek Skoda from the University of Basel’s Department of Biomedicine. “The mutation reprograms the gene product so that it gains a new function and is misused to overproduce EPO.” With consequences for the patients, who suffer from headaches and dizziness thanks to the increased red blood mass.
Mutations in the EPO gene should be taken into account in future searches for the causes of hereditary erythrocytosis, write the researchers in The New England Journal of Medicine.
Jakub Zmajkovic, Pontus Lundberg, Ronny Nienhold, Maria L. Torgersen, Anders Sundan, Anders Waage, and Radek C. Skoda
A Gain-of-Function Mutation in EPO in Familial Erythrocytosis
The New England Journal of Medicine (2018), doi: 10.1056/NEJMoa1709064
Prof. Dr. Radek Skoda, University of Basel, Department of Biomedicine / University Hospital Basel, tel. +41 61 265 23 24, e-mail: firstname.lastname@example.org
Cornelia Niggli | Universität Basel
Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Health and Medicine
16.11.2018 | Life Sciences
16.11.2018 | Life Sciences