Sickle Cell Disease ... (sickle cell disease) (sickle cell disease) - Gen HBB.
Sickle cell disease (sickle cell) is a group of disorders involving hemoglobin. People with this disorder have hemoglobin molecules atypical called hemoglobin S, which can distort the blood erythrocytes, which acquire a sickle or a crescent.
Signs and symptoms of the disease usually begin in early childhood. The characteristic features of this disorder include anemia, repeated infections and periodic episodes of pain. The severity of symptoms varies from person to person. Some people have mild symptoms, while others are frequently hospitalized for more serious complications. The rapid breakdown of red blood cells can also cause jaundice. The painful episodes occur when sickled red blood cells, which are rigid and inflexible, get stuck in small blood vessels. These episodes deprive tissues and organs of blood oxygenation, damaging organs, especially the lungs, kidneys, spleen and brain. A particularly serious complication of the disease is pulmonary hypertension, which occurs approximately one - third of adults with the disease and can lead to heart failure.
This process is due to mutations in the HBB gene, located on the short arm of chromosome 11 (11p15.5), encoding the protein beta-globin. This is a beta-globin subunit of hemoglobin found in blood erythrocytes. Hemoglobin usually consists of four subunits, two beta-globin subunits and two subunits of alpha-globin. Each of the four subunits of the hemoglobin protein carries a molecule containing iron (heme). Heme are necessary for blood erythrocytes collect oxygen in the lungs and transported throughout the body. A complete hemoglobin molecule is capable of carrying four oxygen molecules at once, one for each heme. A mutation HBB gene produces an abnormal version beta-globin known as hemoglobin S (HbS). Other mutations in the gene, leading to a beta-globin additional abnormal version such as hemoglobin C (HBc) and hemoglobin E (HbE). Other mutations HBB gene can result in an unusually low concentration of beta-globin.
In people with sickle cell disease (sickle cell), at least one of the subunits of beta-globin from hemoglobin is replaced with hemoglobin S. In other types of the disease, only one subunit of beta-globin hemoglobin is replaced with S. hemoglobin subunit beta-globin other is replaced with a different variant abnormal, such as hemoglobin C. abnormal versions of beta-globin can distort the blood erythrocyte sickling acquire. Erythrocytes with this sickle die prematurely, causing anemia. Sometimes cells inflexible, sickle block small blood vessels and may cause serious complications.
In sickle cell anemia, the mutation changes one amino acid in the beta-globin, in particular, the amino acid is replaced by glutamic amino acid valine in position 6 (Glu6Val or E6V). Substituting glutamic acid for valine causes abnormal HbS subunits sticking together forming long and rigid molecules.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with sickle cell disease (sickle cell), by complete PCR amplification of exons HBB gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).