Overlap has been reported between the inherited PXE phenotype associated with ENPP1, ABCC6 or NT5E mutations and acquired PXE clinical manifestations associated with haemoglobinopathies induced by HBB mutations.
Background Thalassemia is a common hereditary anemia in humans, and beta thalassemia represents a group of recessively inherited hemoglobin disorders first described by Cooley and Lee and characterized by the abnormal synthesis of β-globin chain.
A full understanding of the molecular mechanisms of epigenetic silencing of HbF expression should facilitate the development of more effective treatment of β-globin chainhemoglobinopathies.
Recent experimental evidence suggest that besides genomic variation within the human β-globin gene cluster, other variants in modifier genes residing outside the human β-globin gene cluster are significantly associated with response to hydroxyurea treatment in β-type hemoglobinopathies patients, deducted from the increase in fetal hemoglobin levels.
In the present study, we investigated how these pathways are used in β-thalassemia, a common hemoglobinopathy in which β-globin gene mutations cause the accumulation and precipitation of cytotoxic α-globin subunits.
Structure analysis was performed on the key mutations that occur in the native protein coded by the HBB gene that causes hemoglobinopathies such as: HbC (E→K), HbD (E→Q), HbE (E→K) and HbS (E→V).
We have confirmed the efficiency of this approach with the identification of beta-globin gene point mutation, which results in the reduced production of globin in an inherited hemoglobin disorder thalassemia disease.
Automated fluorescence-based DNA sequence analysis provides a rapid and reliable method for identification of common, rare and unknown beta-globin gene mutations, which is essential for prevention and control of thalassemia and hemoglobinopathy in Thailand.
Our purpose was to develop and evaluate isolation and enrichment of fetal erythroblasts and a nested polymerase chain reaction (PCR) approach using fetal erythroblasts for detecting the beta-globin gene mutations for a noninvasive prenatal diagnosis of hemoglobinopathies.
The PCR-SSCP technique might be a useful molecular technique to minimize the requirement of direct genomic sequencing to identify beta-globin gene mutations and could be applied in several developing countries where resources are limited but genetic hemoglobin disorders are highly prevalent.
The hematological data of these unusual cases of hemoglobinopathy are presented and compared with a simple heterozygote for Hb Korle-Bu found in another unrelated Thai family. beta-Globin gene haplotype linked to the Thai beta(Korle-Bu) and a simple DNA assay based on allele-specific PCR for rapid diagnosis of Hb Korle-Bu are also described.
This report describes the use of whole-blood spots on filter papers from newborn hemoglobinopathy screening for beta-globin gene cluster haplotyping by the polymerase chain reaction.
The discovery that mutant beta-globin genes arise on different chromosomal backgrounds has allowed studies of the origin and spread of some of the common haemoglobinopathies.
Because of the general nature of these polymorphisms, which are related to the beta-globin gene and its variants only because of their proximity on chromosome 11, they are potentially useful in the prenatal diagnosis of any beta-chain hemoglobinopathy.