Clinical Presentation and Molecular Identification of Four Uncommon Alpha Globin Variants in Thailand

Alpha thalassemia is the most common genetic disease in the world with the prevalence of carriers ranging from 5-50% in several populations. Coinheritance of two defective alpha-globin genes usually gives rise to a symptomatic condition, hemoglobin (Hb) H disease. Previously, it has been suggested from several studies in different populations that nondeletional Hb H disease (--/alpha T alpha or --/alpha alpha(T)) is generally more severe than the deletional type (--/-alpha). In this report, we describe four rare nondeletional alpha-thalassemia mutations in Thai individuals, including initiation codon mutation (HBA2:c.1delA), donor splice site mutation (IVSI-1, HBA1:c.95 + 1G>A), Hb Queens Park (HBA1:c.98T>A) [alpha 32(B13)Met>Lyst and Hb Westmead (HBA2:c.369C>G) [alpha 122(H5)His>GIn]. Interactions of the first three mutations with the alpha(0)-thalassemia resulted in nondeletional Hb H disease; however, their clinical presentations were rather mild and some were detected accidentally. This suggests that a genotype-phenotype correlation of alpha-thalassemia syndrome might be more heterogeneous and so the type of mutation does not simply imply the prediction of the resulting phenotype. Our data will be of use in future genetic counseling of such conditions that are increasingly identified thanks to the improvement of molecular analysis in routine laboratories. (C) 2013 S. Karger AG, Basel