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Vincenzo De Sanctis


Thalassemia distribution



Background: Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. ? -thalassaemia is characterised by the reduced synthesis (? +) or absence (? o) of the ?-globin chains in the HbA molecule, resulting in accumulation of  excess unbound ?-globin chains that precipitate in erythroid precursors in the bone marrow and in the mature erythrocytes, leading to ineffective erythropoiesis and peripheral haemolysis. Approximately 1.5% of the global population are heterozygotes (carriers) of the ?-thalassemias: there is a high incidence in populations extending from the Mediterranean basin throughout the Middle East, the Indian subcontinent, Southeast Asia, Melanesia and into the Pacific Islands

Aim: The principal aim of this paper is to review, from a historical standpoint, our knowledge about an ancient disease, the ?-thalassemias, and  in particular, when, how and in what way ?-thalassemia spread worldwide to reach such high incidences in certain populations.



Results: Mutations involving the ß-globin gene are the most common cause of genetic disorders  in humans. To date, more than 350 ? -thalassaemia mutations have been reported. Considering the current distribution of ?- thalassemia, the wide diversity of mutations and the small number of individual population’s specific mutations, it seems unlikely that ?-thalassemia originated in a single place and time.

Conclusions: Various processes are known to determine the frequency of genetic disease in human populations. However, it is almost impossible to decide to what extent each process is responsible for the presence of a particular genetic disease. The wide spectrum of ?-thalassemia mutations could well be explained by looking at its geographical distribution, the history of malaria, wars, invasions, mass migrations, consanguinity and settlements. The analysis of the molecular spectrum and distribution of haemoglobinopathies allows for the development and improvement of diagnostic tests and management for these disorders.


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