Beta-thalassemia pathophysiology: Difference between revisions
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* '''Nondeletion forms''': These defects generally involve a single base substitution or small deletion or inserts near or upstream of the β globin gene. Most commonly, mutations occur in the promoter regions preceding the beta-globin genes. Less often, abnormal splice variants are believed to contribute to the disease. | * '''Nondeletion forms''': These defects generally involve a single base substitution or small deletion or inserts near or upstream of the β globin gene. Most commonly, mutations occur in the promoter regions preceding the beta-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 (β<sup>o</sup>) or hereditary persistence of fetal hemoglobin syndromes. | * '''Deletion forms''': Deletions of different sizes involving the β globin gene produce different syndromes such as (β<sup>o</sup>) or hereditary persistence of fetal hemoglobin syndromes. | ||
The severity of the disease depends on the nature of the mutation. | |||
* Mutations are characterized as (β<sup>o</sup>) if they prevent any formation of β chains. | |||
* Mutations are characterized as (β<sup>+</sup>) if they allow some β chain formation to occur. | |||
* Alleles without a mutation that reduces function is characterized as (β). (Note that the "+" in β<sup>+</sup> is relative to β<sup>o</sup>, not β.) | |||
In either case there is a relative excess of α chains, but these do not form tetramers: rather, they bind to the [[red blood cell]] membranes, producing membrane damage, and at high concentrations they form toxic aggregates. | |||
==References== | ==References== | ||
Revision as of 16:27, 21 September 2012
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
Genetics
The genetic mutations present in β thalassemias are very diverse, and a number of different mutations can cause reduced or absent β globin synthesis. Two major groups of mutations can be distinguished:
- Nondeletion forms: These defects generally involve a single base substitution or small deletion or inserts near or upstream of the β globin gene. Most commonly, mutations occur in the promoter regions preceding the beta-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.
The severity of the disease depends on the nature of the mutation.
- Mutations are characterized as (βo) if they prevent any formation of β chains.
- Mutations are characterized as (β+) if they allow some β chain formation to occur.
- Alleles without a mutation that reduces function is characterized as (β). (Note that the "+" in β+ is relative to βo, not β.)
In either case there is a relative excess of α chains, but these do not form tetramers: rather, they bind to the red blood cell membranes, producing membrane damage, and at high concentrations they form toxic aggregates.