Primary+Familial+and+Congenital+Polycythemia

By Kristina DiMartino
 * __ Primary Familial and Congenital Polycythemia __**

__** What is PFCP? **__ Primary familial and congenital polycythemia (PFCP) is a rare disease that creates an excess production of erythrocytes (red blood cells). It is inherited in an autosomal dominant matter, which means that only one copy of the gene is needed for the disease to be inherited Specifically it causes a mutation in the //EPOR// erythropoietin receptor gene. Patients with PFCP can experience an increase of up to 50% in the oxygen-carrying capacity of the blood.

The //EPOR// gene provides instructions for making a protein known as the erythropoietin receptor, which is found on the surface of certain blood-forming cells in bone marrow. Erythropoietin is a hormone that directs the production of new red blood cells to carry oxygen to organs and tissues. Mutations in the //EPOR// gene cause the erythropoietin receptor to be turned on for an abnormally long time after attaching to erythropoietin. The overactive receptor signals the production of red blood cells even when they are not needed, which results in an excess of these cells in the bloodstream. Depending on which gene is altered PFCP can be defined as types ECYT1 through ECYT4. When the disease is caused by mutations in the //EPOR// gene, it is known as ECYT1. When it results from //VHL// gene mutations it is known as ECYT2; when the condition is caused by //EGLN1// gene mutations it is called ECYT3; and when the condition results from //EPAS1// gene mutations it is known as ECYT4.
 * __ What is EPOR? __**



Famous, Finnish, Olympic skier, Eero Mäntyranta was diagnosed with this disease and it is believed to have given him an advantage in the Olympic games due to abundance of oxygen in his blood. It was because of this incredible athlete that Finnish scientists studied Mäntyranta and his family. Unlike some athletes today who participate in gene doping, Mäntyranta’s superhero like endurance was due to his genetics. Almost 20 years after Mäntyranta’s retirement, Finnish geneticist Albert de la Chapelle found the single DNA letter swap in Mäntyranta's EPO receptor gene. Today this mutation is colloquially referred to as the “sports gene.”
 * __ Historical Background __**

Many people live never knowing that they may have this disease, but some symptoms include increased redness in the skin, fatigue, shortness of breath, enlarged spleen, excess bleeding, and headaches. Some complications associated with the disease include blood clots, stomach bleeding, heart failure, and gout.
 * __ Symptoms/Complications __**



There is no cure for this disease but in order to prevent blood thickening one pint of blood is removed on a weekly basis, a method known as phlebotomy. In other cases that display abnormal levels of white blood cells and platelets as well as red blood cells, chemotherapy treatments are used. An easier treatment is a daily dose of aspirin but that also has the potential of increasing your risks of stomach bleeding.
 * __ Treatments __**

Current research is investigating the structural requirements for generation of increased Epo sensitivity associated with truncated human EPOR expression and PFCP. Specifically, the ability of the membrane-proximal domain of a truncated human EPOR mutant and its cytoplasmic tyrosine residues to transduce intracellular signals in response to Epo was examined.
 * __ Current Research __**