Silent β-thalassemia mutations at -101 (C>T) and -71 (C>T) and their coinheritance with the sickle cell mutation in...

Silent β-thalassemia (β-thal) is a group of mutations affecting the β-globin gene that cannot be differentiated in heterozygote states from normal conditions by using conventional criteria for the diagnosis of β-thal trait. Here we report the existence of two silent β-thal mutations in the population of Bahrain, one at -101 (C>T) and the other at -71 (C>T). We screened 126 healthy individuals with high-normal Hb A2 levels and found a frequency of 23.0% for both of these mutations (8.0% for -71 and 15.0% for -101). Heterozygotes for either of these two mutations have an overlapping level of Hb A2 ranging from 3.1-3.9% (3.7 ± 0.3) with some cases displaying microcytic and hypochromic anemia, mainly attributed to coinherited defective α-thal genes. Interestingly, each of these mutations were discovered in combination with the sickle cell allele displaying distinct high performance liquid chromatography (HPLC) profiles, different from those observed in the typical sickle cell disease or the sickle cell trait conditions. These investigations are invaluable to provide appropriate counseling for partners undergoing premarital counseling and to understand the molecular basis of mild and atypical forms of sickle cell disease.