Clinical presentation of thalassemia major usually occurs between 6 and 24 months of life, with severe microcyticnormocytic anemia, mild jaundice, and hepatosplenomegaly. The severity of the damage depends on the type of the mutation. Different people will have different symptoms, based on which type of beta thalassemia is inherited. Blood transfusions are required for betathalassemia intermedia and major, but are associated with iron overload complications. Thalassemia trait, also called thalassemia minor, is when a person carries the.
Treatment of beta thalassemia may include medicines and regular blood transfusions. A variety of thalassemia phenotypes can result from simultaneous inheritance of two different thalassemia mutations from each parent or coinheritance of thalassemia together with structural hemoglobin variants 12. As a compensatory mechanism, gamma chain synthesis is increased, resulting in a significant amount of fetal hemoglobin hbf in the blood, which is homogenously distributed in red blood cells. To determine the chromosomal background of beta thalassemia mutations in western iran we studied beta globin gene cluster haplotypes in 314 beta thal and 70 beta a chromosomes with a kurd ethnic. Molecular genetic confirmatory testing from newborn 41. When there isnt enough hemoglobin, the bodys red blood cells dont function properly and they last shorter periods of time, so there are fewer healthy red blood cells traveling. The different types of betathalassemia mutation produce clinical and hematological phenotypes of variable severity even in betacarriers the identi. The role of hfe mutations on iron metabolism in beta. The spectrum of betathalassemia mutations in taiwan.
Mouse models are proving to be useful in assessing the potential of gene therapy. The beta globin gene hbb gene is located on the short arm of chromosome 11. Jun 18, 2018 beta thalassemia major and beta thalassemia intermedia are usually inherited in an autosomal recessive manner, which means both copies of the hbb gene in each cell have mutations. Thalassemia can coexist with other hemoglobinopathies. The second patients cells contained a significant amount of a 20 nucleotide rna species, not initially evident in normal cells, from which part but not all of the large intervening sequence had been removed. Beta thalassemia is caused by changes mutations in the hbb gene while alpha thalassemia is caused by mutations in the hba1 andor hba2 genes. Dec 12, 2011 when there is a mutations in the hbb gene, it prevents the production of any betaglobin.
Most beta thalassemia cases are caused by a mutation in the hemoglobin subunit beta hbb gene, which provides instructions for making beta globin. The hematological diagnosis is based on reduced hemoglobin level beta thalassemia is caused by mutations in the hemoglobin beta hbb gene. Dec 10, 2019 thalassemias are inherited blood disorders. The absence of betaglobin is referred to as beta zero b0 thalassemia. Laboratory diagnosis of thalassemia brancaleoni 2016.
Pdf abstract thalassemia s are genetic disorders inherited from a persons parents. In thalassemia, the production of either the alpha or beta chains are reduced, resulting in either alpha thalassemia or beta thalassemia. Beta thalassemia belongs to a group of diseases called beta hemoglobinopathies, which are caused by mutations in the betaglobin hbb gene 1. Spectrum of severity from asymptomatic to severe anemia and skeletal changes. A study of the molecular lesions of beta thalassemia in lebanon revealed the presence of eight different mutations in 25 patients with cooleys anemia. Oli screening samples for the common africanamerican, asian gonucleotide screening of beta thalassemia mutations in the indian, southeast asian. Betathalassemia prevalence, pathophysiology and inheritance. Mutations may be either in the betaglobin gene itself, or in the promoter for the gene located toward the 5 end. Heterozygous betathalassemia betathalassemia trait homozygous betathalassemia. The red blood cell count rbc and the derived indices are extremely. Over 200 diseasecausing hbb gene mutations have been identified, most of. Blood transfusions are required for beta thalassemia intermedia and major, but are associated with iron overload complications. The betaglobin gene hbb gene is located on the short arm of chromosome 11. Beta thalassemia is an inherited blood disorder in which the body doesnt make hemoglobin normally.
Laboratory diagnosis of hemoglobinopathies and thalassemia. May 21, 2010 beta thalassemia associated with other hb anomalies. Mutations that prevent cells from producing any betaglobin result in betazero b0 thalassemia. The abnormal hemoglobin can lead to anemia not enough rbcs in the body and other medical problems. Betathalassemia symptoms, diagnosis and treatment bmj. Transfusiondependence is one essential factor in distinguishing the various thalassemia phenotypes and their severity. Betathalassemia major and betathalassemia intermedia are usually inherited in an autosomal recessive manner, which means both copies of the hbb gene in each cell have mutations. Genetic syndrome of ineffective erythropoiesis caused by mutations of the betaglobin gene. The symptoms of thalassemia major generally appear before a childs second birthday. Thousands of infants with beta thalassemia are born each year. Deltabeta thalassemia is a rare hemoglobinopathy characterized by decreased production or total absence of delta and betaglobin.
In lebanon, beta thalassemia is the predominant genetic defect. The parents of a person with an autosomal recessive condition each carry one copy of the mutated gene and are referred to as carriers. Jan 01, 2015 beta thalassemia is caused by changes mutations in the hbb gene while alpha thalassemia is caused by mutations in the hba1 andor hba2 genes. Currently, severe thalassemia is treated by blood transfusions, and a minority of patients are cured by bone marrow transplantation. Thalassemia genetic and rare diseases information center. Hemoglobin consists of four protein subunits, typically two subunits of betaglobin and two subunits of. Some mutations beta zero prevent any formation of beta chains.
If one parent has beta thalassemia trait and the other parent has normal hemoglobin a, there is a 50 percent 1 in 2 chance with. In beta thalassemia, the gene for making beta globin chains doesnt work normally. The interaction of hbe and beta thalassemia results in thalassemia phenotypes ranging from a condition indistinguishable from thalassemia major to a mild form of thalassemia intermedia. Mutations that result in complete lack of expression of the gene are termed betazero mutations. This leads to a reduction in the number and ability of the red blood cells. In the severe form of the disease, the bone marrow expands as it attempts. Genotypephenotype correlation among betathalassemia and betathalassemiahbe disease in thai children.
Both are inherited in an autosomal recessive manner. The clinical manifestations include hemolytic anemia and impaired iron handling, the severity of which depends on the degree of impairment in beta globin production. Indeed, the delineation of the impact of these mutations on mrna and protein expression provided the paradigm for the identification of mutations causing other diseases. Seventyfour betathalassemia genes from 37 unrelated betathalassemiamajor patients were systematically characterized by using pcr, dotblot hybridization, and direct sequencing of amplified genomic dna. Betathalassemia trait minor is usually asymptomatic and is associated with the inheritance of a single gene defect. An individual who inherits one copy of a recessive beta thalassemia mutation is a carrier and.
Betathalassemia mutations based on bioinformatics bioedit. Beta thalassemia trait and beta thalassemia disease. Pdf abstract thalassemias are genetic disorders inherited from a persons parents. Betathalassemia is inherited as an autosomal recessive disease. The mutations that cause the thalassemia syndromes were the first to be defined at the level of their dna structure. Mean values of biochemical iron markers were analyzed in beta thalassemia carriers according to their hfe genotype, and all individuals carrying hfe gene. Evolution of a genetic disease in an ethnic isolate. Molecular genetics of the thalassemia syndromes uptodate.
Hemoglobin is a protein that carries oxygen to the body. Treatment depends on the type and severity of the condition but may include blood transfusions andor folic acid supplements. Full text genotypephenotype correlation among beta. Beta thalassemia trait is also known as beta thalassemia minor. Betathalassemia major results in severe transfusion dependent anemia and is caused by the inheritance of two betaglobin gene mutations either in. Other mutations increasing hbf production are those associated with deletional and nondeletional hpfh linked to the beta globin gene cluster.
Beta thalassemia trait when you have one working copy of the beta globin gene and one nonworking copy you have beta thalassemia trait. Sunni muslims had the highest beta thalassemia carrier rate and presented the greatest heterogeneity, with 16 different mutations. Beta thalassemia is inherited as an autosomal recessive disease. Your body makes less of the beta chains, but is still able to make plenty of. Beta thalassemia mechanism of disease beta thalassemia is a rare, inherited blood disorder characterized by low levels of hemoglobin, which resides in red blood cells and carries oxygen throughout the body. Genetic diversity of betathalassemia mutations in pakistani population article in journal of the pakistan medical association 509.
Genetic basis of beta thalassemia encoding genes on chromosome 11 short arm each cell contains 2 copies of beta globin gene beta globin protein level alpha globin protein level suppression of gene more likely than deletion 2 mutations. Beta thalassemia is usually inherited in an autosomal recessive manner, which means both copies of the hbb gene in each cell have mutations. Thalassemia is due to a deficit or absent production of. Beta thalassemia is, in most cases, an autosomal recessive disease. Beta thalassemia major is a clinical diagnosis referring to a patient who has a severe form of the disease and requires chronic transfusions early in life. As with about half of all hereditary diseases, an inherited mutation damages the assembly of the messengertype rna mrna that is transcribed from a chromosome. Specific populations generally carry a small number of mutations, the most common of which are those that are widely distributed regionally. Normally, beta thalassemia trait does not cause any health problems.
In beta thalassemia, symptoms occur starting from six to 24 months of age. Dna contains both the instructions genes for stringing amino acids together into proteins, as well as stretches of dna. Beta thalassemia trait is inherited from ones parents, like hair or eye color. Thalassemia quantitative a quantitative decrease in the production of alpha or beta globin chain large deletions, point mutations, small insertiondeletion that leads to decreased transcription or an unstable transcript beta thalassemia results from mutations in beta genes pathogenesis a result of the free alpha subunits. Although most of the molecular lesions involve the structural. Delta thalassemia an overview sciencedirect topics. Nonsense mutations and frameshift mutations tend to not produce any. Betathalassemia mutations and haplotype analysis in lebanon. Beta thalassemia is a hereditary disease affecting hemoglobin. Nov 22, 2019 the mutations associated with thalassemia are passed from parents to children. Our data thus indicate that mutations which affect rna processing cause.
Depending on the severity of symptoms three categories may be identified. Thalassemia major is the most severe form of beta thalassemia. Thalassemia is due to decreased production of at least one globin polypeptide chain beta, alpha, gamma, delta which results in unbalanced hemoglobin synthesis. Individuals with beta thalassemia minor have a mutation in one hbb gene, while individuals with the intermediate and major forms have mutations in both hbb genes. Genetic syndrome of ineffective erythropoiesis caused by mutations of the beta globin gene. Beta thalassemia occurs most frequently in people from mediterranean countries, north africa, the middle east, india, central asia, and southeast asia. As well as alpha and beta chains present in hemoglobin, about 3% of adult hemoglobin is made of alpha and delta chains. Hemoglobin consists of four protein subunits, typically two subunits of beta globin and two subunits of another protein called alphaglobin. Beta thalassemia is an inherited hemoglobinopathy in which the production of one or both beta globin chains is impaired. The hbb gene provides instructions for making a protein called beta globin. The hematological diagnosis is based on reduced hemoglobin level beta thalassemia is a fairly common blood disorder worldwide. Feb 24, 2015 genetic basis of beta thalassemia encoding genes on chromosome 11 short arm each cell contains 2 copies of beta globin gene beta globin protein level alpha globin protein level suppression of gene more likely than deletion 2 mutations. The hbb gene provides instructions for making a protein called betaglobin. Aug 23, 2018 thalassemia is a blood disorder that is caused by dna mutations in cells that are responsible for producing haemoglobin.
Other hbb gene mutations allow some betaglobin to be produced but in reduced amounts. Betathalassemia genetic and rare diseases information. Beta thalassemia results from decreased production of beta polypeptide chains. Beta thalassemia was the first described in 1925, by thomas cooley, a detroit pediatrician, who reported on children of italian origin who presented with severe microcytic anemia and other red cell abnormalities see image below, enlarged liver. Just as with beta thalassemia, mutations that affect the ability of this gene to produce delta chains can occur. Hemoglobin molecules are made of chains called alpha and beta chains that can be affected by mutations. The betathalassemias were among the first human genetic diseases to be examined by means of new techniques of recombinant dna analysis. The most frequently encountered mutation was ivs 1. In general, the molecular pathology of disorders resulting from mutations in the nonalphaglobin gene region is the best known 7. Over 200 diseasecausing hbb gene mutations have been identified, most of which are point mutations. Thalassemias occur most often among people of italian, greek, middle eastern, southern asian, and african descent. Depending on the type of beta thalassemia, symptoms. Hemoglobin is the part of red blood cells rbcs that carries oxygen throughout the body.