Genotypic-Phenotypic Diversity in Beta Thalassemia
The remarkable variability in clinical severity of the thalassemia reflects both genetic and environmental factors. It is becoming apparent that the genetic element involves many loci, some of which are directly involved with the basic defect in globin synthesis, whereas others, which modify or dete...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
PAGEPress Publications
2014-08-01
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| Series: | Mediterranean Journal of Hematology and Infectious Diseases |
| Subjects: | |
| Online Access: | https://mjhid.org/index.php/mjhid/article/view/1689 |
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| Summary: | The remarkable variability in clinical severity of the thalassemia reflects both genetic and environmental factors. It is becoming apparent that the genetic element involves many loci, some of which are directly involved with the basic defect in globin synthesis, whereas others, which modify or determine the variable complications of the disease, have nothing to do with globin. Thus genetic determinants of the thalassemia are the many different mutations of the ?-globin genes that underlie ?-thalassemia; secondary, loci that are also involved in globin synthesis(? globin gene); and tertiary, loci that are not involved in globin production but that might modify the complications of the disease in many different ways. There are two main varieties of ? thalassemia alleles; ?0 thalassemia in which no ? globin is produced, and ?+ thalassemia in which some ? globin is produced, but less than normal. Less severe forms are sometimes designated ?++ to reflect the minimal deficit in ? chain production. The mild ?+ thalassemia alleles are associated with clearly defined changes in heterozygotes and result in disorders of intermediate severity in homozygotes. The co-inheritance of different ?-thalassemia alleles might reduce the severity of the homozygous or compound heterozygous states for ?0 thalassemia to some degree and can convert the severe forms of ?+ thalassemia into milder, non-transfusion-dependent conditions. Other genetic markers such as Xmn1, HPFH, the occurrence of gamma-globin gene triplications and a number of cis-elements, like motifs in the -530 bp position 5? to beta-globin gene cap site, other motifs in the LCR (locus control region) of the beta-globin locus, or the pre-G-gamma haplotypes and the intragenic A-gamma-delta globin genes haplotypes are also need to be determining in predicting severity of the disease. Few genetic variability at loci which does not directly modify the overall degree of globin chain imbalance but may have important phenotypic effect, in particular related to some of the complications of the disease. Genes governing the hyperbilirubinemia (UGT1A1), Iron overload (HFE), skeletal deformity and bone diseases (VDR, COL1A1& COL1A2), hypercoagulable state (FVL, PT& MTHFR) and cardiac complications (Apo E, GST) may also have predictable role in increasing phenotypic complexity in thalassemia patients. |
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| ISSN: | 2035-3006 |