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Beta Hemoglobinopathies Genetic Testing

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Beta Hemoglobinopathies Genetic Testing BETA HEMOGLOBINOPATHIES GENETIC TESTING • The stiff, sickle-shaped cells can get stuck inside small What are beta blood vessels, which can prevent blood from flowing into or out of organs and tissues. This can lead to hemoglobinopathies? health problems ranging from episodes of pain to Beta hemoglobinopathies are inherited recurring infections to serious organ damage. disorders caused by the abnormal production Complications of sickle cell disease usually develop in of hemoglobin in the blood. Hemoglobin is early childhood and may include the following3,4: a protein found in red blood cells that carries • Anemia oxygen from the lungs to all parts of your body. • Painful swelling of the hands and feet If the molecular structure of hemoglobin is • Yellowing of the skin (jaundice) abnormal, or if there is not enough hemoglobin • Recurring infections in your blood, your organs and tissues may • Blockage of blood vessels in the spleen causing not receive enough oxygen. This can result in enlargement and restriction of blood flow (splenic symptoms of anemia, which include tiredness sequestration) (fatigue), weakness, shortness of breath, and • Recurrent pain crises (severe pain in the arms, legs, pale skin. Anemia may lead to more severe head, chest, abdomen, or back) complications, such as organ damage, that may • High blood pressure in the lungs (pulmonary be life threatening. hypertension) causing shortness of breath, chest pain, and a rapid heart rate • Blockage of blood vessels in the brain, which can lead Beta hemoglobinopathies are most common in to stroke people of African, Asian, Hispanic, Italian, Middle Blockage of blood vessels in the lungs (acute chest 1,2 • Eastern, West Indian, and Mediterranean descent. syndrome) causing shortness of breath, cough, chest Examples of these disorders include sickle cell disease pain, and fever and beta-thalassemia. When diagnosed and treated early, some of the health problems caused by beta What is beta thalassemia? hemoglobinopathies may be prevented.2 Beta-thalassemia leads to reduced production of hemoglobin, and affected people also have a shortage of What is sickle cell disease? mature red blood cells that are able to deliver oxygen to Sickle cell disease is caused by the presence of abnormal organs and tissues. Beta thalassemia is classified into 2 hemoglobin molecules in red blood cells. Sickle cell types: thalassemia major (also known as Cooley’s anemia) anemia, a common type of sickle cell disease, is caused is a severe form, and thalassemia intermedia is a less by the presence of an abnormal hemoglobin molecule severe form.5,6 called hemoglobin S. Children with thalassemia major typically develop signs Red blood cells that contain normal hemoglobin and symptoms during the first 2 years of life.5,6 They have molecules are disc-shaped and flexible. Those containing severe anemia, which can become life threatening if not hemoglobin S have an abnormal, sickle shape (like a treated. Other complications may include5,6: crescent moon or the letter C) and are stiff and sticky. • Jaundice • Sickle-shaped red blood cells break apart easily, which leads to a shortage of red blood cells to carry oxygen • Poor weight gain and growth (failure to thrive) to organs and tissues. This is the cause of anemia. • Feeding problems BETA HEMOGLOBINOPATHIES | GENETIC TESTING • Irritability • A complete blood count (CBC) is typically the first test • Recurrent fevers done to identify people with anemia who may benefit from additional testing to find out if they have a beta Enlarged abdomen due to enlargement of the spleen • hemoglobinopathy. (hepatomegaly) • A blood test called hemoglobin electrophoresis can Misshapen bones resulting from expansion of bone • identify the amount and types of hemoglobin (such marrow as hemoglobin S) present in a person’s blood and may People who have thalassemia intermedia may develop help identify of people who need more testing to signs and symptoms during childhood or later in life. diagnose thalassemia disorders. Their anemia may be mild to moderately severe, and they Genetic tests for HBB mutations are available and may be may also have growth delays and bone abnormalities.6 used to confirm a diagnosis of a beta hemoglobinopathy, What causes beta hemoglobinopathies? identify carriers of HBB mutations, or determine whether a Beta hemoglobinopathies are caused by abnormal developing baby (fetus) is affected. changes in certain genes. Genes are found in every cell • HBB full gene sequencing is a procedure that reads the in your body. They carry the instructions for making instructions (DNA) that make up the HBB gene. This is proteins that control how each of your cells work. Genes a way to identify the presence of an altered HBB gene can undergo abnormal changes (called mutations) that in a person’s cells, which may help a doctor confirm the may cause cells to stop working the way they should. diagnosis of a beta hemoglobinopathy. Gene mutations may result in health problems, and they Duplication/deletion testing is a way to find out may be passed from parent to child (inherited). • whether the HBB gene contains mutations resulting Beta hemoglobinopathies are caused by mutations in the from the presence of extra (duplicated) or missing beta-globin (HBB) gene, which instructs cells to make a (deleted) parts of DNA code. protein called beta-globin. Normal hemoglobin consists The above tests can be performed on: of 2 beta-globin subunits and 2 alpha-globin subunits. • A sample of blood. • Certain HBB mutations lead to the production of • Cells obtained by swabbing the inside of the mouth hemoglobin S, which causes sickle cell disease. (buccal swab). • Some HBB mutations lead to decreased production • Prenatal samples of amniotic fluid (the watery of beta-globin. Others prevent cells from making any substance that surrounds a fetus) or the chorionic villi beta-globin at all. These are the mutations that cause (a small piece of tissue taken from the placenta). beta thalassemia. Beta hemoglobinopathies are inherited in an autosomal Who should be tested for HBB gene mutations? 4-6 recessive manner. This mean a child needs to inherit 2 The American College of Obstetricians and Gynecologists copies of an HBB mutation (1 from each parent) in order (ACOG) recommends offering beta hemoglobinopathy to be affected. The severity and age of onset of beta carrier testing for people planning a pregnancy if they are hemoglobinopathies vary from person to person. These of African, Southeast Asian, or Mediterranean descent.1 differences may be related to the specific combination It is also important for you to inform your health care of HBB gene mutations present and whether any other provider if anyone in your family has or is a carrier of any 2,6 globin genes are mutated. To date, hundreds of HBB of these conditions. Additionally, ACOG recommends mutations have been identified, not all of which have genetic counseling if both parents are found to be carriers 7 been linked with health problems. of beta hemoglobinopathies.1 A person who inherits 1 copy of an HBB mutation is What possible results of full gene sequencing can a “carrier” and is not expected to have related health be reported and what do they mean? problems. Carriers of sickle cell disease may be described Negative: After scanning the HBB gene, no detectable 3 • as having sickle cell trait. Carriers of beta thalassemia mutations were found. This test does not detect all may be described as having beta thalassemia minor (and possible mutations in the gene. For this reason, a 5 may have mild anemia). When both parents are carriers negative result cannot completely rule out the of HBB mutations, each of their children will have a 1 in 4 presence of a gene mutation that is causing a person's 2 chance of being affected with a beta hemoglobinopathy. symptoms. How are beta hemoglobinopathies diagnosed? • Positive – Abnormal: After scanning the HBB gene, • Newborns are tested for beta hemoglobinopathies.2,3 2 mutations were found. Along with a person's signs BETA HEMOGLOBINOPATHIES | GENETIC TESTING and symptoms, a positive genetic test result may Where can I find more information? confirm a diagnosis of a beta hemoglobinopathy. If you have questions or want more information about • Positive – Carrier: After scanning the HBB gene, 1 genetic testing for beta hemoglobinopathies, ask your mutation was found. It is likely that this person is a doctor or genetic counselor. You may search for a genetic carrier of a beta hemogoblinopathy. This person may counselor in your area using an online address book benefit from genetic counseling to discuss how his/her provided by the National Society of Genetic Counselors at carrier status may affect family planning, testing of his/ www.nsgc.org. her reproductive partner, and testing of at-risk family Other information resources include: members. • Variant of unknown significance: After scanning • Centers for Disease Control and Prevention the HBB gene, a mutation was found that has not Home page: www.cdc.gov been reported before. It is unclear if the mutation • Genetics Home Reference is the cause of a person's signs and symptoms. Home page: http://ghr.nlm.nih.gov Genetic testing of family members may provide more • March of Dimes information. If all affected family members have the Telephone: (914) 997-4488 same mutation, then it is likely to be linked to the Home page: www.marchofdimes.com inherited disorder. If some affected family members do not have the mutation, it is less likely to be linked to the disorder. Full gene sequencing test results should be combined with clinical findings and reviewed by a heath professional who specializes in medical genetics. Note: This material is provided for general information purposes only. It is not intended as a substitute for medical advice and/or consultation with a physician or technical expert.
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