Genetic Testing for Hemophilia

Hemophilia results from a defect in the genetic material of the body. This genetic material is called deoxyribonucleic acid, or DNA. Any part of the DNA that controls an inherited trait is called a gene. Examples of inherited traits are eye color, hair color and blood type.

The most common forms of hemophilia result from defects in the genes that control the production of clotting factors VIII or IX.

Genes are present within the cell in packages called chromosomes. Most of the body's cells contain a complete copy of chromosomes and their genes. Among the chromosomes people inherit from their parents are two sex chromosomes, labeled X and Y. All males receive the X chromosome from their mother and the Y chromosome from their father. Females have two X chromosomes, one inherited from each parent.

The genes that control the production of the clotting factors VIII and IX are located in the X chromosome.

Males (XY) have hemophilia when the gene for clotting factor VIII (hemophilia A, classical hemophilia) or clotting factor IX (hemophilia B, Christmas disease) on the single X chromosome is affected.

Women (XX) who are carriers generally don't have symptoms of hemophilia because only one X chromosome has a copy of the hemophilia gene. The other gene of the other X chromosome allows for normal production levels of clotting factors VIII or IX. Those women who have only one affected gene are called hemophilia carriers. Not all males with hemophilia have mothers who are carriers. Sometimes a mutation (a genetic change) occurs resulting in hemophilia. Currently, it is not known why this mutation happens.

Sons of women who carry the hemophilia gene have a 50 percent chance of inheriting the gene and having hemophilia. Daughters of women who are carriers have a 50 percent chance of also being carriers of hemophilia. In families where only one male is known to have hemophilia, it is usually possible to determine whether the hemophilia gene was passed from a mother who carries the gene or whether a new mutation occurred in the person with hemophilia.

The Hemophilia Center at Cincinnati Children's Hospital Medical Center can perform genetic testing and counseling for hemophilia.

As part of genetic counseling, a physician or genetic counselor will take a family history and draw a family tree, called a pedigree. The pedigree generally includes three generations: children, parents, aunts, uncles, cousins and grandparents. The pedigree helps identify people within the family who could be carriers of the gene. Women who are possible carriers of hemophilia could then choose to be tested.

For hemophilia A and B, it is possible to look for mutations within the gene. This approach is called direct DNA testing and is the most accurate method for identifying carriers. A blood sample from the male family member with hemophilia is checked first. In about 98 percent of cases, a mutation can be identified. Next, a blood sample from the woman desiring carrier testing is obtained, and her DNA is checked for the specific mutation. Such testing is performed at specialized laboratories. Results are generally available in several weeks. 

In some cases of hemophilia A and Hemophilia B, a mutation cannot be identified. However, it may be possible to use indirect or linkage tests to determine the gene carrier status of females by tracking the gene in the family. Blood samples are obtained from the male with hemophilia and other family members. Patterns of linked DNA in the person with hemophilia are compared to the DNA in family members to check for the same pattern. Linkage testing is not as accurate as direct testing and does not provide information for all families. The genetic counselor will discuss these issues individually with families.

Because women rarely show symptoms of hemophilia, they can be carriers of the disorder without knowing it. Women related to a male with hemophilia, such as a mother, sister, aunt, or cousin on the mother's side, can be carriers and may want to have carrier testing. The daughters of a male with hemophilia are always carriers of hemophilia.

A women's decision about carrier testing or how she chooses to use that information can be influenced by many factors. These factors include the severity of the hemophilia that occurs in her family and her own desires and beliefs, as well as those of her partner. Women who are considering having children may find it most beneficial to have carrier testing before becoming pregnant. Females typically are tested for carrier status when they are old enough to make an informed decision, normally in the late teens or older.

A woman with a family history of hemophilia A or B may wish to have the fetus tested during pregnancy. Making the decision to pursue prenatal screening is a personal choice and involves many factors. The risks and benefits of prenatal screening should be discussed with an obstetrician or genetic counselor.

During the 10th or 12th week of pregnancy, an outpatient test called chorionic villus sampling can be performed. A small amount of the developing placenta is obtained for testing. Another outpatient procedure called an amniocentesis can be performed after 13 weeks of pregnancy. During the amniocentesis, a small amount of fluid containing fetal cells is removed and tested for hemophilia if the fetus is male (XY).

For additional information about genetic testing or genetic counseling, contact the Division of Human Genetics, 513-636-4760. 

Genetic Testing for Hemophilia is a good idea.

Genetic Testing for Hemophilia

Sons of women who carry the hemophilia gene have a 50 percent chance of inheriting the gene and having hemophilia.

Last Updated 12/2013