De Sanctis Vincenzo, Kattamis Christos, Canatan Duran, Soliman Ashraf T, Elsedfy Heba, Karimi Mehran, Daar Shahina, Wali Yasser, Yassin Mohamed, Soliman Nada, Sobti Praveen, Al Jaouni Soad, El Kholy Mohamed, Fiscina Bernadette, Angastiniotis Michael
Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy.
First Department of Paediatrics, University of Athens, Athens, Greece.
Mediterr J Hematol Infect Dis. 2017 Feb 20;9(1):e2017018. doi: 10.4084/MJHID.2017.018. eCollection 2017.
Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. β-thalassaemia is characterised by the reduced synthesis (β) or absence (β) of the β-globin chains in the HbA molecule, resulting in accumulation of excess unbound α-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 β-thalassemias; there is a high incidence in populations from the Mediterranean basin, throughout the Middle East, the Indian subcontinent, Southeast Asia, and Melanesia to the Pacific Islands.
The principal aim of this paper is to review, from a historical standpoint, our knowledge about an ancient disease, the β-thalassemias, and in particular, when, how and in what way β-thalassemia spread worldwide to reach such high incidences in certain populations.
Mutations involving the β-globin gene are the most common cause of genetic disorders in humans. To date, more than 350 β-thalassaemia mutations have been reported. Considering the current distribution of β- thalassemia, the wide diversity of mutations and the small number of specific mutations in individual populations, it seems unlikely that β-thalassemia originated in a single place and time.
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 β-thalassemia mutations could well be explained by looking at their geographical distribution, the history of malaria, wars, invasions, mass migrations, consanguinity, and settlements. An analysis of the distribution of the molecular spectrum of haemoglobinopathies allows for the development and improvement of diagnostic tests and management of these disorders.
血红蛋白病是全球最常见的隐性单基因疾病,对患者的治疗给全球带来了沉重的疾病负担。β地中海贫血的特征是HbA分子中β珠蛋白链合成减少(β+)或缺失(β0),导致过量未结合的α珠蛋白链积累,这些链在骨髓中的红系前体细胞和成熟红细胞中沉淀,导致无效造血和外周溶血。全球约1.5%的人口是β地中海贫血的杂合子(携带者);在地中海盆地、中东、印度次大陆、东南亚以及从美拉尼西亚到太平洋岛屿的人群中发病率很高。
本文的主要目的是从历史角度回顾我们对一种古老疾病——β地中海贫血的认识,特别是β地中海贫血何时、如何以及以何种方式在全球传播,从而在某些人群中达到如此高的发病率。
涉及β珠蛋白基因的突变是人类遗传疾病最常见的原因。迄今为止,已报道了350多种β地中海贫血突变。考虑到β地中海贫血的当前分布、突变的广泛多样性以及个体人群中特定突变的数量较少,β地中海贫血似乎不太可能起源于单一的地点和时间。
已知多种过程决定人类群体中遗传疾病的频率。然而,几乎不可能确定每个过程在何种程度上导致了特定遗传疾病的出现。通过研究β地中海贫血突变的地理分布、疟疾历史、战争、入侵、大规模迁徙、近亲结婚和定居点等因素,可以很好地解释β地中海贫血突变的广泛谱系。对血红蛋白病分子谱系分布的分析有助于开发和改进这些疾病的诊断测试及管理方法。