Multiple Minisequencing Screen for Seven Southeast Asian Nondeletional α-Thalassemia Mutations

[摘要] α-Thalassemia is the most common globin disorder in the world, and the severe forms are especially prevalent among Southeast Asians. It is a disorder of absent or reduced production of α-globin chains resulting from mutations in the α-globin gene cluster on chromosome 16p13.3. Most α-thalassemia mutations involve deletions of one (−α) or both (− −) α-globin genes, whereas point mutations within the α-globin genes (αTα or ααT) are much less frequent. Nonetheless, the number of point mutations that have been described has been steadily increasing, with >40 identified to date (1)(2).The importance of nondeletional α-thalassemia mutations is underscored by the observation that patients with nondeletional hemoglobin (Hb) H disease (αTα/− −) are generally more severely affected and more likely to require transfusions compared with deletional Hb H disease patients (−α/− −) (3). There have also been a few reports of Hb H disease caused by homozygosity or compound heterozygosity of nondeletional mutations involving the α2-globin gene (αTα/αTα) (1)(3). Additionally, nondeletional Hb H disease involving the α2 codon 30 or codon 59 mutation can cause the fatal Hb H hydrops fetalis syndrome, especially if associated with large ζ-α-globin gene deletions (4). In certain regions of Southeast Asia, nondeletional Hb H disease can account for as many as 50% of all Hb H disease patients (3).Several specific and reliable molecular tests have previously been developed to diagnose and screen the most common deletional (5)(6) and nondeletional (7)(8) α-thalassemia mutations. We now describe a multiplex minisequencing assay to detect seven Southeast Asian nondeletional mutations: Hb Constant Spring (α2 codon 142 TAA→CAA), Hb Paksé (α2 codon 142 TAA→TAT), Hb Quong Sze (α2 codon 125 CTG→CCG), α2 codon 0 Δ1bp (−T), α2 …

[学科分类] 过敏症与临床免疫学