The coinheritance of Hb Lepore defects with β-thalassemic alleles results in variable clinical severity transfusion-dependent thalassemia depending on the different degree of globin imbalance and compensatory HbF production. Severe clinical conditions similar to β-thalassemia major were observed in Hb Lepore homozygote subjects. Hb analysis shows 5%–15% of Hb Lepore and increased HbF levels that in most cases do not exceed 5%.
The Hb Lepore carriers display a β-thalassemic phenotype with microcytosis and hypochromia. In all Hb Lepore variants, the synthesis of the δβ hybrid chain is significantly lower than that of the β-chain, resulting in an overall reduction in non- α-globin chains. It has been found with a low frequency in a variety of ethnic groups, mainly in Mediterranean countries. Hb Lepore Boston Washington is the most common Lepore variant. Two further δβ-Lepore variants, Hb Lepore-Leiden (complex rearrangement) and Hb Lepore ARUP ( δ31/ β50), were recently described with a single case report for each. Three Hb Lepore variants were characterized several years ago, each with a different crossover breakpoint: Hb Lepore Boston Washington ( δ87/ β116), Hb Lepore Hollandia ( δ22/ β50), and Hb Lepore Baltimore ( δ50/ β86) (HbVar database: ). The δβ hybrid globin chain contains the amino terminal sequence of δ-globin fused to the carboxyterminus of the β-chain. The high sequence homology between - and β-globin genes favors this type of recombination that results in the deletion of approximately 7.4 kb. Under the name of Hb Lepore, a small group of structurally abnormal Hbs that result from in-frame fusion between the 5′ end of the δ-globin gene and the 3′ end of the β-globin gene is defined, formed by unequal crossover or gene conversion events during meiosis. The knowledge of the spectrum of mutations associated with different geographical areas is the prerequisite to set up large-scale screening programs and be able to offer genetic counseling to couples at risk. This latter allowed us to define the correct structure of the hybrid δβ-globin gene. The diagnostic procedure implies hematological, biochemical, and molecular analysis, including multiplex ligation-dependent probe amplification (MLPA) assay, GAP-PCR, and DNA sequencing.
The patient, a 10-year-old child, shows severe anemia with a Hb level of 6.85 g/dL and typical thalassemic red cell indices. Here, we describe the first occurrence of Hb Lepore Boston Washington in a Syrian individual. It includes some of the few clinically significant Hb variants that are associated with a β-thalassemia phenotype. The Hb Lepore is widespread all over the world and in many ethnic groups. Hemoglobin (Hb) Lepore is composed of two normal α chains and two δβ fusion globins that arise from unequal crossover events between the δ- and β-globin genes.
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