Mutations Two major groups of mutations can be distinguished: * Nondeletion forms: These defects, in general, involve a single base substitution or small insertions near or upstream of the β globin gene. Most often, mutations occur in the promoter regions preceding the<unk> -globin genes. Less often, abnormal splice variants are believed to contribute to the disease. * Deletion forms: Deletions of different sizes involving the β globin gene produce different syndromes such as (βo) or hereditary persistence of fetal hemoglobin syndromes. Mutations are characterized as (βo) if they prevent any formation of β globin chains, mutations are characterized as (β+) if they allow some β globin chain formation to occur. Name Older synonyms Description Alleles Heterozygous form: Only one of β globin alleles bears a mutation. Individuals will suffer from microcytic anemia. Detection usually involves lower than normal mean corpuscular volume value (+/ββo/β Affected individuals can often manage a normal life but may need occasional transfusions, e.g., at times of illness or pregnancy, depending on the severity of their anemia. β+/β+βo/β+ Mediterranean anemia; Cooley anemia Homozygous form: Occurs when both alleles have<unk> assemia mutations. This is a severe microcytic, hypochromic anemia. Untreated, it causes anemia, splenomegaly and severe bone deformities, and progresses to death before age 20. Treatment consists of periodic blood transfusion; splenectomy for splenomegaly and chelation of transfusion-related iron overload. βo/βo mRNA assembly Protein HBB PDB 1a00: this is a healthy<unk>  Globin Protein<unk>  is a hereditary disease affecting hemoglobin. As with about half of all hereditary diseases, an inherited mutation damages the assembly of the messenger-type RNA (mRNA) that is transcribed from a chromosome. DNA contains both the instructions (genes) for stringing amino acids together into proteins, as well as stretches of DNA that play important roles in regulating produced protein levels. In<unk> assemia, an additional, contiguous length or a discontinuous fragment of non-coding instructions is included in the mRNA. This happens because the mutation obliterates the boundary between the intronic and exonic portions of the DNA template. Because all the coding sections may still be present, normal hemoglobin may be produced and the added genetic material, if it produces pathology, instead disrupts regulatory functions enough to produce anemia. Hemoblogin's normal alpha and<unk>  subunits each have an iron-containing central portion (heme) that allows the protein chain of a subunit to fold around it. Normal adult hemoglobin contains 2 alpha and 2<unk>  subunits.<unk> assemias typically affect only the mRNAs for production of the<unk>  chains (hence the name). Since the mutation may be a change in only a single base (single-nucleotide polymorphism), on-going efforts seek gene therapies to make that single correction.
Beta thalassemia
Thalassemia
Delta-beta thalassemia
Alpha-thalassemia
Sickle cell-beta thalassemia
Paroxysmal nocturnal hemoglobinuria
Diamond–Blackfan anemia
Hereditary spherocytosis