By: Siobhan, Gabby, Michela, Kristine and Brianne
Where is the gene located?
What type of mutation causes the disorder?
More than 1,300 alterations in the F8 gene have been identified to cause Hemophilia A and more than 900 in the F9 have been identified to cause Hemophilia B. One type of mutation is substitution which changes single DNA building blocks (base pairs) in the gene. Substitution is less common in the F8 gene and more prominent in the F9 gene. Others are frame shift mutations that delete or insert multiple base pairs and chromosomal mutations that rearranges large segments of genetic material called an inversion. Both of these make up a small percentage of mutations in the F9 gene, however, inversions are most common in the F8 gene for people who have severe Hemophilia A.
What is the function of the protein the gene codes for?
function of the f8 gene
provides instructions for making a protein called coagulation factor VIII
Coagulation factors are a group of related proteins that are essential for the formation of blood clots.
Coagulation factor VIII is made chiefly by cells in the liver
this protein circulates in the bloodstream .
What effect does the mutation have on the structure of the protein the gene codes for?
One which is easy to understand is caused by changing a single base at the beginning of a codon for argenine (CGA) somewhere in the gene to give TGA. If you look back to the table higher up the page, you will find that TGA is a stop codon. missense muatation
What is the mechanism of the disorder (what effects does the alteration in function of the protein have on the workings of the cell and the body)?
The mechanism is called the blood coagulation process, which transforms the blood from a liquid to a solid; it involves several different clotting factors. The mechanism makes fibrin when it is activated, which together with the platelet plug, stops the bleeding.
if coagulation factors are missing or low, the blood does not clot properly and bleeding continues
patients with Hemophilia A or B have a genetic defect, resulting in a deficiency in one of the blood clotting factors
Diagram of the wild type and mutated type protein and the pathway
Signs and symptoms
Prolonged bleeding after getting a cut, removing a tooth, or having surgery
Bleeding into muscles and joints, especially the knees, elbow, and ankles
Frequent and prolonged nosebleeds
Can the disorder be treated?
Hemophilia can be treated by replacing the missing clotting factor in the blood. This type of therapy is known as the factor replacement therapy. Clotting factor replacement therapy is carried out by infusing the clotting factor concentrates into a vein, much like a blood transfusion. The essential blood clotting proteins are Factor VIII, which is needed to treat Hemophilia A and Factor IX, which is needed to treat Hemophilia B. Bleeding stops when enough clotting factors reach the bleeding site, so it is very important that treatment is given as fast as possible to avoid long-term damage. Some products involve factor concentrates, cryoprecipitate, plasma, and whole blood which are responsible in improving blood clotting. Unfortunately, the replacement of the missing clotting factors is not permanent. Half of the clotting factor activity which was infused is removed by the body every 12 to 24 hours. This means that within 2 or 3 days almost none is left. The hemophiliac's blood is again unable to clot normally.