Contributions
Abstract: PB2492
Type: Publication Only
Background
Non homologous crossing-over between d and β globin genes results in a family of fusion genes that produce the Lepore and anti Lepore type hemoglobins. The Lepore hemoglobins are characterized by globins chains with a δ-amino terminus, a β-carboxyl terminus, and reduced synthesis, resembling that seen in normal δ synthesis. The reciprocal products of the Lepore genes, the anti Lepore type hemoglobins (Miyada, Hong Kong, CHORI…), have β-amino and δ carboxyl terminal and also exhibit reduced synthesis. In other hand the hemoglobin Parchman is a rare variant that hybrid globin chain had a δ-amino terminus, an internal β-chain fragment, and a δ-carboxyl terminus.
Aims
We present a new hemoglobin, the result of a double cross-linking of the δ and β genes or an unequal cross-linking between a Lepore type gene and the β gene. The new fused globin chain has the β-amino end, an internal δ chain fragment and the β carboxy terminus and its synthesis is similar to that of β-globin.
Methods
The propositus was an 80-year-old white man for the hemoglobinopathies study, because to rule out type 2 diabetes, Hb A1c was quantified by ion exchange HPLC (Variant II turbo) and an abnormal peak appeared in a retention time (RT) of 1.15 min which constituted 43.9%. Analysis of hemoglobins was made by HPLC exchange ionic (Variant II), electrophoresis capillary (Sebia Capillarys Flex) and the DNA analysis using PCR; MLPA and automatic sequencing of Sanger of δ and β genes.
Results
Sequencing showed that the 5 'end belongs to the HBB gene up to CD8, from CD9 and up to CD31 to the HBD gene and since the reverse sequencing of the β gene established that from the 3' UTR region and up to CD32 it belonged to the gene HBB, an unequal crossover between the HBD and HBB genes should have been carried out, causing a crossover gene reversion of at least 196 bp and a maximum of 225 bp of the HBD gene in the HBB gene which would give rise to a βδβ hybrid gene. This uncertainty would be due to the fact that although the sequence up to +21 from Cap belongs to the HBB gene, from this position and up to CD8 it could correspond to both the HBB gene and the HBD since this sequence is completely the same in both genes. This recombination probably took place during meiosis.
Conclusion
In the case of this new variant (Hb Palencia), it is probably the result of a cross-linking between a Lepore type gene (Baltimore or Washington-Boston) and a HBB gene, since the probability of a double cross-linking of the genes HBD and HBB in a region that covers less than 200 bp is extremely low. The normal levels of Hb A2 (2.9%) suggest that in both chromosomes the HBD gene would be intact, allowing a correct synthesis of the δ-globin chain. On the other hand, the percentage of Hb Palencia, around 40%, is similar to that of Hb A, therefore, the synthesis of the βδβ-globin chain should be controlled in a similar way to that of β-globin. And since the propositus does not have a thalassemia phenotype, consequently the β cluster of one chromosome would be strictly normal and that of the other allele would have a normal HBD gene and the β would correspond to the hybrid (βδβ).This Hb Palencia is the first variant due to a hybrid gene, constituted in the 3 'and 5' UTR ends by the sequences and machinery of the HBB gene and a part of the interior by sequences of the HBD gene. This structure would confirm that the sequences of the promoter regions as well as those of the IVS-II are necessary and essential for the synthesis of the β-globin type chain.
Session topic: 28. Thalassemias
Keyword(s): Hemoglobin
Abstract: PB2492
Type: Publication Only
Background
Non homologous crossing-over between d and β globin genes results in a family of fusion genes that produce the Lepore and anti Lepore type hemoglobins. The Lepore hemoglobins are characterized by globins chains with a δ-amino terminus, a β-carboxyl terminus, and reduced synthesis, resembling that seen in normal δ synthesis. The reciprocal products of the Lepore genes, the anti Lepore type hemoglobins (Miyada, Hong Kong, CHORI…), have β-amino and δ carboxyl terminal and also exhibit reduced synthesis. In other hand the hemoglobin Parchman is a rare variant that hybrid globin chain had a δ-amino terminus, an internal β-chain fragment, and a δ-carboxyl terminus.
Aims
We present a new hemoglobin, the result of a double cross-linking of the δ and β genes or an unequal cross-linking between a Lepore type gene and the β gene. The new fused globin chain has the β-amino end, an internal δ chain fragment and the β carboxy terminus and its synthesis is similar to that of β-globin.
Methods
The propositus was an 80-year-old white man for the hemoglobinopathies study, because to rule out type 2 diabetes, Hb A1c was quantified by ion exchange HPLC (Variant II turbo) and an abnormal peak appeared in a retention time (RT) of 1.15 min which constituted 43.9%. Analysis of hemoglobins was made by HPLC exchange ionic (Variant II), electrophoresis capillary (Sebia Capillarys Flex) and the DNA analysis using PCR; MLPA and automatic sequencing of Sanger of δ and β genes.
Results
Sequencing showed that the 5 'end belongs to the HBB gene up to CD8, from CD9 and up to CD31 to the HBD gene and since the reverse sequencing of the β gene established that from the 3' UTR region and up to CD32 it belonged to the gene HBB, an unequal crossover between the HBD and HBB genes should have been carried out, causing a crossover gene reversion of at least 196 bp and a maximum of 225 bp of the HBD gene in the HBB gene which would give rise to a βδβ hybrid gene. This uncertainty would be due to the fact that although the sequence up to +21 from Cap belongs to the HBB gene, from this position and up to CD8 it could correspond to both the HBB gene and the HBD since this sequence is completely the same in both genes. This recombination probably took place during meiosis.
Conclusion
In the case of this new variant (Hb Palencia), it is probably the result of a cross-linking between a Lepore type gene (Baltimore or Washington-Boston) and a HBB gene, since the probability of a double cross-linking of the genes HBD and HBB in a region that covers less than 200 bp is extremely low. The normal levels of Hb A2 (2.9%) suggest that in both chromosomes the HBD gene would be intact, allowing a correct synthesis of the δ-globin chain. On the other hand, the percentage of Hb Palencia, around 40%, is similar to that of Hb A, therefore, the synthesis of the βδβ-globin chain should be controlled in a similar way to that of β-globin. And since the propositus does not have a thalassemia phenotype, consequently the β cluster of one chromosome would be strictly normal and that of the other allele would have a normal HBD gene and the β would correspond to the hybrid (βδβ).This Hb Palencia is the first variant due to a hybrid gene, constituted in the 3 'and 5' UTR ends by the sequences and machinery of the HBB gene and a part of the interior by sequences of the HBD gene. This structure would confirm that the sequences of the promoter regions as well as those of the IVS-II are necessary and essential for the synthesis of the β-globin type chain.
Session topic: 28. Thalassemias
Keyword(s): Hemoglobin