Reliable Detection of β-Thalassemia and G6PD Mutations by a DNA Microarray

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Abstract
β-Thalassemia is an autosomal recessive disorder caused by the absence or reduction of β-globin chain synthesis. There are >400 million β-thalassemia carriers worldwide, and >160 β-thalassemia mutations have been described (1). Different populations exhibit a specific subset of mutations, as in Sardinia, where carriers are ∼11% of the population and 95% of them present the β0 39 mutation (1)(2)(3). In those populations, glucose 6-phosphate dehydrogenase (G6PD) deficiency is also common (4)(5)(6). For the G6PD gene, ∼130 mutations or combinations of mutations have been described (7), and early detection might reduce the risk of hemolytic crisis in childhood. A program of screening newborns would be desirable in those populations. The molecular diagnosis of β-globin and G6PD mutations currently involves a combination of classic methodologies such as restriction fragment length polymorphism analysis, allele-specific oligonucleotide (ASO) hybridization, reverse dot blots, amplification refractory mutation system (ARMS), and direct sequencing (2)(8)(9)(10)(11). These methods are laborious for large-scale screening.