Hemophilia

The genetic disorder which I have chosen as the subject of my report is hemophilia. There are two types of hemophilia, hemophilia-A and hemophilia-B. The clinical symptoms of both are very similar so for the purposes of this paper I have chosen to concentrate on hemophilia-A.

Hemophilia-A is an X linked bleeding disorder resulting from a defect in a protein known as coagulation factor VIII. Since the disorder is X linked it is expressed mainly in males, who must have mothers who are carriers. Females who express the disorder must have affected fathers and mothers who are carriers, or who are affected. The level of severity of the disorder breeds true in any given family, which indicates that the phenotypic expression of the disorder reflects the genetic defect. In about 5% of cases, hemophilia-A results from partial deletion of the factor VIII gene, and is severe. Other cases result from a single base mutation in the gene. This can result in nonsense mutations which result in premature stop codons, and a severe expression of the disorder, or missense mutations which cause milder forms of the disorder. In some cases the disorder can also result from spontaneous mutations, but this is less common.

The gene for hemophilia-A is located at Xq28 while the gene for hemophilia-B is located at Xq27.1-q27.2. There are about thirty other disorders associated with the Xq28 area including manic depression and favism. This must indicate that Xq28 includes many different genes which have not yet been isolated.

The primary symptom of hemophilia is uncontrolled bleeding. The disease can range in severity from a mild increase in bleeding, to massive bleeding from even a minor wound. Treatment involves blood or clotting factor transfusions, and this increases the risk of contracting HIV, hepatitis or other blood transmitted diseases. Since blood banks have started screening and treating blood for HIV, the infection rate has dropped to almost nothing. However,prior to 1985 almost half the hemophiliac population was infected with HIV.

Defects in the factor VIII gene are so numerous in type that doctors cannot easily test for each one of them. By doing a series of genetic tests a definitive answer can be given about 60 to 80 percent of the time. By combining the genetic tests with a blood test, this percentage rises to about 80 to 90 percent. Recently a single defect was found which is thought to account for about half of the more severe cases of hemophilia.